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14. Abstract of papers Pharmaceutical and Biomedica Analysis Meeting

Author

Beysens, A. J., Beuman, G. H., van der Heijden, J. J., Hoogtanders, K. E. J., Steijqer, O. M., Lingeman, H., Bosman, J., Ensing, K., Franke, J. P., Hartstra, J., de Zesuw, R. A., de Fluiter, P., Jansen, E. H. J. M., Hoebus, J., Yun, Li Ming, Hoogmartens, J., Janssen, P. S. L., Langenhuizen, M. H. J. M., Kaijser, G. P., Beijnen, J. H., Jeunink, E., Underberg, W. J. M., Khan, K., Paesen, J., Roets, E., Lorreyne, W., Van Rompaey, F., Woestenborghs, R., Heykants, J., Hendrix, C., De Beer, J., Crommen, J., Van den Bossche, W., Porqueras, E., Hooqmartens, J., van Gijn, R., Koks, C. H. W., Rosing, H., Spruijt, M. P. N., Meenhorst, P. L., Burger, P. M., van Tellingen, O., Thoithi, G., Van Schepdael, A., Herdewijn, P., Pauwels, C., Geuens, I., Cornelissen, L., Van Roosbroeck, D., Macken, E., Van Aerschot, A., Vendrig, D. E. M. M., Gout, E., van der Voorden, E. C., van Hulten, O. L. T., Wafelman, A. R., Hoefnagel, C. A., Witte, D. T., Ahnoff, M., Franke, J. -P., de Zeeuw, R. A., and Yongxin, Zhu

Published
1993
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21. Abstracts of papers Pharmaceutical and biomedical analysis meeting

Author

Bandhoe, A. U., Paalman, A. C. A., Underberg, W. J. M., Beijnen, J. H., Bekers, O., Otagiri, M., Bult, A., Beuman, Gert, van der Heijden, Jacques, Janss, Jenny, Ceelen, P. R. J., Feenstra-Bielders, G. G. L. M., Groeneveld, D. J., de Boer, D., Rutten, M. J. A., de Jong, E. G., Maes, R. A. A., van Rossum, J. M., de Groot, G., Kopps, R., Savelkoul, T. J. F., van Vloten, P., de Jonag, E. G., van Ooyen, R., Kiffers, J., de Kroon, I. F. I., Langendijk, P. N. J., de Goede, P. N. F. C., De Smet, M., Musch, C., Peeters, A., Buydens, L., Massart, D. L., De Turck, K., Cachet, Th., Hoogmartens, J., Delrue, M., Lannoo, P., Drenth, B. F. H., Beckeringh, F. J., Bosman, J., Feitsma, K. G., van Nijhuisvan Dam, A., Driebergen, R. J., van Gorp, J. A., Ensing, K., Farlam, A., de Jong, G. J., Frel, R. W., Brinkman, U. A. Th., Gerding, T. K., van de Grampel, V. J. M., Niemeijer, N. R., de Zeeuw, R. A., Tepper, P. G., Horn, A. S., Halvax, J. J., Wiese, G., van Bennekom, W. P., Hindriks, Rik, Buydens, Lutgarde, Peeters, Anne, de Smet, Marina, Massart, Luc, Blokland, Aric, Vink, Jan, Keizers, S., de Jong, E. G., Niessen, W. M. A., Verhey, E. R., LaVos, G. F., Tjaden, U. R., van der Greef, J., Ooms, J. A., Haak, G. S. J., Grooten, G., Pattyn, G., Sandra, P., David, F., van Oosterom, A. T., de Bruijn, E. A., Pouwelse, A. V., de Jong, D., Lammers, N. G. F. M., van den Berg, J. H. M., Quintens, I., Roets, E., Reeuwijk, H. J. E. M., Lingeman, H., Keizer, H. J., Rosing, H., Elferink, F., van de Vaart, F. J., Kloeg, P. H. A. M., Sauter, André, Stegehuis, D. S., Reinhoud, N. J., Steijger, O. M., Hilhorst, J. J. L., Holthuis, J. J. M., Underberg-Chitoe, U. K., Meenhorst, P. L., Van den Mooter, G., Hauchecorne, R., Vinckier, C., van der Horst, A., Martens, H. J. M., van der Horst, F. A. L., Post, M. H., van Ginkel, L. A., Zoontjes, P. W., van Blitterswijk, H., Stephany, R. W., van Gijn, R., Bakker, C. H., Koks, C. H. W., Rodenhuis, S., van Opstal, M. A. J., van den Horst, F. A. L., Krabbenborg, P., van Tellingen, O., Woude, H. R. v. d., van Beers, C. J. T., Nooyen, W. J., Varossieau, F. J., Los, G., Nagel, J. D., McVie, J. G., Veen, R. N., Land, J. T. Op 't, Vendrig, D. E. M. M., Teeuwsen, J., Verlaar, F. C. A. M., Trum, T. J. H. M., de Kleijn, J. P., Vervoort, R., Vrieling, M., Maris, F., Hindriks, H., Walhagen, A., Edholm, L. -E., Heeremans, C. E. M., and van der Hoeven, R. A. M.

Published
1989
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22. Nevirapine plus didanosine: once or twice daily combination?

Author

van Heeswijk, R. P., Veldkamp, A. I., Mulder, J. W., Meenhorst, P. L., Wit, F. W., Reiss, P., Lange, J. M., Kwakkelstein, M. O., Beijnen, J. H., Hoetelmans, R. M., Amsterdam institute for Infection and Immunity, Global Health, and Other departments

Subjects
Infectious Diseases, Pharmacology (medical)
Published
2000

23. Importance of baseline prognostic factors with increasing time since initiation of highly active antiretroviral therapy: collaborative analysis of cohorts of HIV-1-infected patients

Author

Sterne, Jonathan A. C., May, Margaret, Sabin, Caroline, Phillips, Andrew, Costagliola, Dominique, Chêne, Geneviève, Justice, Amy C., De Wolf, Frank, Hogg, Robert, Battegay, Manuel, Monforte, Antonella D'Arminio, Gerdtkenheuer, Fa, Staszewski, Schlomo, Gill, John, Egger, Matthias, Casabona, Jordi, Dabis, Francxois, Kitahata, Mari, Leport, Catherine, Lundgren, Jens, Reiss, Peter, Saag, Michael, Weller, Ian, Beckthold, Brenda, Yip, Benita, Dauer, Brenda, Fusco, Jenifer, Lanoy, Emilie, Rickenbach, Martin, Lavignolle, Valerie, Van Sighem, Ard, Pereira, Edwige, Pezzotti, Patrizio, Schmeisser, Norbert, Billaud, E., Boué, F., Costagliola, D., Duval, X., Duvivier, C., Enel, P., Fournier, S., Gasnault, J., Gaud, C., Gilquin, J., Grabar, S., Khuong, M. A., Lang, J. M., Mary Krause, M., Matheron, S., Meyohas, M. C., Pialoux, G., Poizot Martin, I., Pradier, C., Rouveix, E., Salmon Ceron, D., Sobel, A., Tattevin, P., Tissot Dupont, H., Yasdanpanah, Y., Aronica, E, Tirard Fleury, V., Tortay, I., Abgrall, S., Guiguet, M., Lanoy, E., Leneman, H., Lièvre, L., Potard, V., Saidi, S., Vildé, J. L., Leport, C., Yeni, P., Bouvet, E., Gaudebout, C., Crickx, B., Picard Dahan, C., Weiss, L., Tisne Dessus, D., Sicard, D., Salmon, D., Auperin, I., Viard, J. P., Roudière, L., Fior, R., Delfraissy, J. F., Goujard, C., Lesprit, P. h., Jung, C., Meynard, J. L., Picard, O., Desplanque, N., Cadranel, J., Mayaud, C., Rozenbaum, W., Bricaire, F., Katlama, C., Herson, S., Simon, A., Decazes, J. M., Molina, J. M., Clauvel, J. P., Gerard, L., Sellier, P., Diemer, M., Dupont, C., Berthé, H., Saïag, P., Mortier, E., Chandemerle, C., De Truchis, P., Bentata, M., Honoré, P., Tassi, S., Jeantils, V., Mechali, D., Taverne, B., Laurichesse, H., Gourdon, F., Lucht, F., Fresard, A., Faller, J. P., Eglinger, P., Bazin, C., Verdon, R., Peyramond, D., Boibieux, A., Touraine, J. L., Livrozet, J. M., Trepo, C., Cotte, L., Ravaux, I., Delmont, J. P., Moreau, J., Gastaut, J. A., Soubeyrand, J., Retornaz, F., Blanc, P. A., Allegre, T., Galinier, A., Ruiz, J. M., Lepeu, G., Granet Brunello, P., Pelissier, L., Esterni, J. P., Nezri, M., Cohen Valensi, R., Laffeuillade, A., Chadapaud, S., Reynes, J., May, T., Rabaud, C., Raffi, F., Pugliese, P., Michelet, C., Arvieux, C., Caron, F., Borsa Lebas, F., Rey, D., Fraisse, P., Massip, P., Cuzin, L., Arlet Suau, E., Thiercelin Legrand, M. F., Sobesky, M., Pradinaud, R., Contant, M., Montroni, M., Scalise, G., Braschi, M. C., Riva, A., Tirelli, U., Cinelli, R., Pastore, G., Ladisa, N., Minafra, G., Suter, F., Arici, C., Pristera, R., Chiodo, F., Colangeli, V., Fiorini, C., Coronado, O., Carosi, G., Cadeo, G. P., Torti, C., Minardi, C., Bertelli, D., Rizzardini, G., Melzi, S., Manconi, P. E., Piano, P., Cosco, L., Scerbo, A., Vecchiet, J., D'Alessandro, M., Santoro, D., Pusterla, L., Carnevale, G., Citterio, P., Viganò, P., Mena, M., Ghinelli, F., Sighinolfi, L., Leoncini, F., Mazzotta, F., Pozzi, M., Lo Caputo, S., Vullo, Vincenzo, Lichtner, Miriam, Angarano, G., Grisorio, B., Saracino, A., Ferrara, S., Grima, P., Tundo, P., Pagano, G., Cassola, G., Alessandrini, A., Piscopo, R., Toti, M., Chigiotti, S., Soscia, F., Tacconi, L., Orani, A., Perini, P., Scasso, A., Vincenti, A., Chiodera, F., Castelli, P., Scalzini, A., Palvarini, L., Moroni, M., Lazzarin, A., Cargnel, A., Vigevani, G. M., Caggese, L., d'Arminio Monforte, A., Repetto, D., Galli, A., Merli, S., Pastecchia, C., Moioli, M. C., Esposito, R., Mussini, C., Abrescia, N., Chirianni, A., Izzo, C. M., Piazza, M., De Marco, M., Viglietti, R., Manzillo, E., Nappa, S., Antonucci, G., Iacomi, F., Narciso, P., Zaccarelli, M., Colomba, A., Abbadessa, V., Prestileo, T., Mancuso, S., Ferrari, C., Pizzaferri, P., Filice, G., Minoli, L., Bruno, R., Novati, S., Baldelli, F., Tinca, M., Petrelli, E., Cioppi, A., Alberici, F., Ruggieri, A., Menichetti, F., Martinelli, C., De Stefano, C., La Gala, A., Ballardini, G., Rizzo, E., Magnani, G., Ursitti, M. A., Arlotti, M., Ortolani, P., Cauda, R., Dianzani, F., Ippolito, G., Antinori, A., D'Elia, S., Petrosillo, N., De Luca, A., Bacarelli, A., Acinapura, R., De Longis, P., Brandi, A., Trotta, M. P., Noto, P., Capobianchi, M. R., Carletti, F., Girardi, E., Pezzotti, P., Rezza, G., Mura, M. S., Mannazzu, M., Caramello, P., Di Perri, G., Soranzo, M. L., Orofino, G. C., Arnaudo, I., Bonasso, M., Grossi, P. A., Basilico, C., Poggio, A., Bottari, G., Raise, E., Ebo, F., De Lalla, F., Tositti, G., Resta, F., Loso, K., Cozzi Lepri, A., Johnson, A. M., Mercey, D., Phillips, A., Johnson, M. A., Mocroft, A., Murphy, M., Weber, J., Scullard, G., Fisher, M., Battegay, M., Bernasconi, E., Böni, J., Bucher, H., Bürgisser, P. h., Cattacin, S., Cavassini, M., Dubs, R., Egger, M., Elzi, L., Erb, P., Fantelli, K., Fischer, M., Flepp, M., Fontana, A., Francioli, P., Hirschel, B., Soravia Dunand, V., Furrer, H., Gorgievski, M., Günthard, H., Kaiser, L., Kind, C., Klimkait, T. h., Lauper, U., Ledergerber, B., Opravil, M., Paccaud, F., Pantaleo, G., Perrin, L., Piffaretti, J. C., Rickenbach, M., Rudin, C., Schmid, P., Schüpbach, J., Speck, R., Telenti, A., Trkola, A., Vernazza, P., Buy, E., Bronsveld, W., Hillebrand Haverkort, M. E., Reiss, P., Back, N. K. T., Bakker, M. E. G., Berkhout, B., Jurriaans, S., Cuijpers, T. h., Rietra, P. J. G. M., Roozendaal, K. J., Pauw, W., Van Zanten, A. P., Smits, P. H. M., Von Blomberg, B. M. E., Savelkoul, P., Danner, S. A., Van Agtmael, M. A., Claessen, F. A. P., Perenboom, R. M., Rijkeboer, A., Van Vonderen, M., Kuijpers, T. W., Pajkrt, D., Scherpbier, H. J., Prins, J. M., Bos, J. C., Eeftinck Schattenkerk, J. K. M., Geerlings, S. E., Godfried, M. H., Lange, J. M. A., Van Leth, F. C., Lowe, S. H., Van Der Meer, J. T. M., Nellen, F. J. B., Pogány, K., Van Der Poll, T., Ruys, T. h. A., Sankatsing, S., Steingrover, R., Van Twillert, G., Van Der Valk, M., Van Vonderen, M. G. A., Vrouenraets, S. M. E., Van Vugt, M., Wit, F. W. M. N., Veenstra, J., Van Eeden, A., Veen, J. H., Van Dam, P. S., Roos, J. C., Brinkman, K., Frissen, P. H. J., Weigel, H. M., Mulder, J. W., Van Gorp, E. C. M., Meenhorst, P. L., Mairuhu, A. T. A., Richter, C., Van Der Berg, J., Van Leusen, R., Swanink, C. M. A., Vriesendorp, R., Jeurissen, F. J. F., Franck, P. F. H., Lampe, A. S., Kauffmann, R. H., Koger, E. L. W., Bravenboer, B., Ten Napel, C. H. H., Kootstra, G. J., Schirm, J., Bennw, C. A., Sprenger, H. G., Miesen, W. M. A. J., Doedens, R., Scholvinck, E. H., Ten Kate, R. W., Van Houte, D. P. F., Polee, M., Kroes, A. C. M., Claas, H. C. J., Kroon, F. P., Van Den, Broek, Van Dissel, J. T., Schippers, E. F., Bruggeman, C. A. M. V. A., Goossens, V. J., Schreij, G., Van De Geest, S., Verbon, A., Galama, J. M. D., Melchers, W. J. G., Poort, Y. A. G., Koopmans, P. P., Keuter, M., Post, F., Van Der Ven, A. J. A. M., Doornum, G. J. J., Niesters, M. G., Osterhaus, A. D. M. E., Schutten, M., Driessen, G., De Groot, R., Hartwig, N., Van Der Ende, M. E., Gyssens, I. C., Van Der Feltz, M., Den Hollander, J. G., De Marie, S., L. Nouwen, J., Rijnders, B. J. A., De Vries, T. E. M. S., Juttmann, J. R., Van De Heul, C., Van Kasteren, M. E. E., Boucher, C. A. B., Schuurman, R., Geelen, S. P. M., Wolfs, T. F. W., Schneider, M. M. E., Bonten, M. J. M., Borleffs, J. C. C., Ellerbroek, P. M., Hoepelman, I. M., Jaspers, C. A. J. J., Schouten, I., Schurink, C. A. M., Blok, W. L., Tanis, A. A., Groeneveld, P. H. P., Jansen, C. L., Hendriks, R., Veenendaal, D., Storm, H., Weel, J., Van Zeijl, J. H., Buiting, A. G. M., Swaans, C. A. M., Boel, E., Jansz, A. F., Losso, M., Duran, A., Vetter, N., Karpov, I., Vassilenko, A., Clumeck, N., Dewit, S., Poll, B., Colebunders, R., Machala, L., Rozsypal, H., Sedlacek, D., Gerstoft, J., Katzenstein, T., Hansen, A. B. E., Skinhøj, P., Nielsen, J., Lundgren, J., Benfield, T., Kirk, O., Pedersen, C., Zilmer, K., Girard, P. M., Saint Marc, T., Vanhems, P., Dabis, F., Dietrich, M., Manegold, C., Van Lunzen, J., Stellbrink, H. J., Staszewski, S., Bickel, M., Goebel, F. D., Fätkenheuer, G., Rockstroh, J., Schmidt, R., Kosmidis, J., Gargalianos, P., Sambatakou, H., Perdios, J., Panos, G., Filandras, A., Karabatsaki, E., Banhegyi, D., Mulcahy, F., Yust, I., Turner, D., Burke, M., Pollack, S., Hassoun, G., Sthoeger, Z., Maayan, S., Borghi, R., Cotugno, A. D., Gabbuti, A., Chiesi, A., Montesarchio, E., Finazzi, R., D'Arminio Monforte, A., Viksna, L., Chaplinskas, S., Hemmer, R., Staub, T., Bruun, J., Maeland, A., Ormaasen, V., Knysz, B., Gasiorowski, J., Horban, A., Prokopowicz, D., Wiercinska Drapalo, A., Boron Kaczmarska, A., Pynka, M., Beniowski, M., Mularska, E., Trocha, H., Antunes, F., Valadas, E., Mansinho, K., Matez, F., Duiculescu, D., Babes, Victor, Streinu Cercel, A., Vinogradova, E., Rakhmanova, A., Jevtovic, D., Mokráš, M., Staneková, D., González Lahoz, J., Sánchez Conde, M., García Benayas, T., Martin Carbonero, L., Soriano, V., Clotet, B., Jou, A., Conejero, J., Tural, C., Gatell, J. M., Miró, J. M., Blaxhult, A., Karlsson, A., Pehrson, P., Weber, R., Kravchenko, E., Chentsova, N., Barton, S., Brettle, R., Loveday, C., Antunes, Francisco, Blaxhult, Anders, Clumeck, Nathan, Gatell, Jose, Horban, Andrzej, Johnson, Anne, Katlama, Christine, Ledergerber, Bruno, Loveday, Clive, Vella, Stefano, Gjørup, I., Friis Moeller, N., Bannister, W., Mollerup, D., Podlevkareva, D., Holkmann Olsen, C., Kjær, J., Raffanti, Stephen, Dieterch, Douglas, Becker, Stephen, Scarsella, Anthony, Fusco, Gregory, Most, Bernard, Balu, Rukmini, Rana, Rashida, Beckerman, Robin, Ising, Theodore, Fusco, Jennifer, Irek, Renae, Johnson, Bernadette, Hirani, Ashwin, Edwinjesus, De, Pierone, Gerald, Lackey, Philip, Irek, Chip, Johnson, Alison, Burdick, John, Leon, Saul, Arch, Joseph, Helm, Eilke B., Carlebach, Amina, Axelller, Mu, Haberl, Annette, Nisius, Gabi, Lennemann, Tessa, Rottmann, Carsten, Wolf, Timo, Stephan, Christoph, Bickel, Markus, Manfredsch, Mo, Gute, Peter, Locher, Leo, Lutz, Thomas, Klauke, Stephan, Knecht, Gabi, Doerr, Hans W., Stu, Martinrmer, Von Hentig, Nils, Jennings, Beverly, Beylot, J., Chêne, G., Dupon, M., Longy Boursier, M., Pellegrin, J. L., Ragnaud, J. M., Salamon, R., Thiébaut, R., Lewden, C., Lawson Ayayi, S., Mercié, P., Moreau, J. F., Morlat, P., Bernard, N., Lacoste, D., Malvy, D., Neau, D., Blaizeau, M. J., Decoin, M., Delveaux, S., Hannapier, C., Labarrère, S., Lavignolle Aurillac, V., Uwamaliya Nziyumvira, B., Palmer, G., Touchard, D., Balestre, E., Alioum, A., Jacqmin Gadda, H., Bonarek, M., Bonnet, F., Coadou, B., Gellie, P., Nouts, C., Bocquentin, F., Dutronc, H., Lafarie, S., Aslan, A., Pistonne, T., Thibaut, P., Vatan, R., Chambon, D., De La Taille, C., Cazorla, C., Ocho, A., Viallard, J. F., Caubet, O., Cipriano, C., Lazaro, E., Couzigou, P., Castera, L., Fleury, H., Lafon, M. E., Masquelier, B., Pellegrin, I., Breilh, D., Blanco, P., Loste, P., Caunègre, L., Bonnal, F., Farbos, S., Ferrand, M., Ceccaldi, J., Tchamgoué, S., De Witte, S., Alexander, Chris, Barrios, Rolando, Braitstein, Paula, Brumme, Zabrina, Chan, Keith, Cote, Helen, Gataric, Nada, Geller, Josie, Guillemi, Silvia, Richard Harrigan, P., Harris, Marrianne, Joy, Ruth, Levy, Adrian, Montaner, Julio, Montessori, Val, Palepu, Anita, Phillips, Elizabeth, Phillips, Peter, Press, Natasha, Tyndall, Mark, Wood, Evan, Bhagani, S., Byrne, P., Carroll, A., Cuthbertson, Z., Dunleavy, A., Geretti, A. M., Heelan, B., Johnson, M., Kinloch de Loes, S., Lipman, M., Madge, S., Marshall, N., Nair, D., Nebbia, G., Prinz, B., Swaden, L., Tyrer, M., Youle, M., Chaloner, C., Grabowska, H., Holloway, J., Puradiredja, J., Ransom, D., Tsintas, R., Bansi, L., Fox, Z., Harris, E., Hill, T., Lampe, F., Lodwick, R., Reekie, J., Sabin, C., Smith, C., Amoah, E., Booth, C., Clewley, G., Garcia Diaz, A., Gregory, B., Labbett, W., Tahami, F., Thomas, M., Read, Ron, Fatkenheuer, G., Schmeisser, N., Voigt, K., Wasmuth, J. C., Wohrmann, A., Infectious diseases, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Medical Microbiology and Infection Prevention, Paediatric Infectious Diseases / Rheumatology / Immunology, Landsteiner Laboratory, ARD - Amsterdam Reproduction and Development, Graduate School, Cardiology, APH - Global Health, APH - Quality of Care, AII - Infectious diseases, AII - Inflammatory diseases, and Global Health

Subjects
Adult, medicine.medical_specialty, AIDS, CD4 counts, Highly active antiretroviral therapy, HIV, Prognosis, Substance abuse (intravenous), Adolescent, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Europe, HIV Infections, HIV-1, Humans, Middle Aged, North America, Risk Factors, Substance Abuse, Intravenous, Survival Analysis, Pharmacology (medical), Infectious Diseases, Cost effectiveness, Antiretroviral Therapy, Article, Acquired immunodeficiency syndrome (AIDS), Internal medicine, medicine, Highly Active, Survival analysis, Immunodeficiency, business.industry, Transmission (medicine), Hazard ratio, Substance Abuse, medicine.disease, Confidence interval, Physical therapy, Intravenous, business, Cohort study
Abstract

Background: The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear. Methods: We analyzed data on 20,379 treatment-naive HIV-1- infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of follow-up, 1844 AIDS events, and 1005 deaths). Results: Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count 350 cells/μL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART). Conclusions: Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART.

Published
2007

25. Steady-state pharmacokinetics of twice-daily dosing of saquinavir plus ritonavir in HIV-1-infected individuals

Author

Veldkamp, A. I., van Heeswijk, R. P., Mulder, J. W., Meenhorst, P. L., Schreij, G., van der Geest, S., Lange, J. M., Beijnen, J. H., Hoetelmans, R. M., and Other departments

Abstract

To compare the steady state plasma pharmacokinetics of 1000 mg of saquinavir (SQV) in a soft-gel capsule (SGC) formulation in combination with 100 mg of ritonavir (RTV) (capsules) in a twice-daily dosing regimen in HIV-1-infected individuals with historical controls who used 400 mg of SQV in a hard-gel capsule (HGC) formulation in combination with 400 mg of RTV and to investigate the plasma pharmacokinetics of the 1000 mg/100 mg regimen after normal and high-fat breakfasts. Open-label, crossover, steady-state pharmacokinetic study. Six HIV-1-infected individuals who used either 1200 mg of SQV (SGC or HGC) three times daily or 400 mg twice daily in combination with 400 mg of RTV twice daily were included. Each patient was switched to 1000 mg of SQV SGC twice daily in combination with 100 mg of RTV twice daily. After 14 days, the patients came to the hospital for assessment of a pharmacokinetic profile during 12 hours. Patients were randomized to receive a high-fat (+/-45 g of fat) or normal (+/-20 g of fat) breakfast. After 7 days, a second pharmacokinetic profile was assessed after ingestion of the drugs with the alternate breakfast. A noncompartmental pharmacokinetic method was used to calculate the area under the plasma concentration versus time curve (AUC0-12h), the maximum plasma concentration (Cmax), the plasma trough concentration (C12h), and the elimination half-life in plasma (t1/2). The obtained pharmacokinetic parameters were compared with those of 12 patients using SQV HGC (400 mg twice daily) in combination with RTV (400 mg twice daily). The median values of the pharmacokinetic parameters for SQV SGC (1000 mg twice daily, normal breakfast) were: AUC0-12h, 18.84 h*mg/L; Cmax, 3.66 mg/L; C12h, 0.40 mg/L; and t1/2, 3.0 hours. The median values of the pharmacokinetic parameters for SQV HGC (400 mg twice daily, normal breakfast) were: AUC0-12h, 6.99 h*mg/L; Cmax, 1.28 mg/L; C12h, 0.23 mg/L; and t1/2, 3.9 hours. The exposure to SQV in the dosing regimen of 1000 mg twice daily in combination with 100 mg of RTV twice daily was significantly higher than the exposure to SQV in a dosing regimen of 400 mg twice daily in combination with 400 mg of RTV twice daily. The pharmacokinetic parameters of SQV SGC in the dosing regimen of 1000 mg twice daily in combination with 100 mg of RTV twice daily were not significantly different after ingestion of a high-fat or normal breakfast (p >.35). The combination of 1000 mg of SQV SGC twice daily and 100 mg of RTV twice daily resulted in a higher exposure to SQV compared with the exposure to SQV obtained when SQV is used in the 400 mg/400 mg twice-daily combination with RTV. In this small number of patients, no significant differences in exposure were seen after ingestion of either a normal or high-fat breakfast. From a pharmacokinetic perspective, the combination of 1000 mg of SQV SGC twice daily and 100 mg of RTV twice daily seems to be a good option for further clinical evaluation

Published
2001

26. Monitoring of epstein-barr virus DNA load in peripheral blood by quantitative competitive PCR

Author

Stevens, S J, Vervoort, M B, van den Brule, A J, Meenhorst, P L, Meijer, C J, Middeldorp, J M, Pathology, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, CCA - Cancer biology, CCA - Cancer immunology, CCA - Biomarkers, CCA - Clinical Therapy Development, CCA - Evaluation of Cancer Care, AII - Cancer immunology, CCA - Target Discovery & Preclinial Therapy Development, and AII - Infectious diseases

Subjects
hemic and lymphatic diseases
Abstract

A competitive quantitative PCR (Q-PCR) assay combined with simple silica-based DNA extraction was developed for monitoring of Epstein-Barr virus (EBV) DNA load in unfractionated peripheral blood. The Q-PCR is based on competitive coamplification of a highly conserved 213-bp region of the EBNA-1 open reading frame with an internal standard (IS), added in a known concentration. The IS has the same amplicon length and base composition as the wild-type (WT) EBNA-1 amplicon but differs in 23 internally randomized bases. Competitive coamplification yields two PCR products that are quantified by enzyme immunoassay or by electrochemiluminescence detection, with probes specific for the 23 differing internal nucleotides. The Q-PCR has a sensitivity of 10 copies of either WT or IS plasmid DNA. The Q-PCR was validated by quantification of known amounts of plasmid containing the WT EBNA-1 target. Furthermore, we determined EBV genome copy numbers in different cell lines. For EBV quantification in clinical samples, DNA was isolated from lysed whole blood by silica-affinity purification. Forty-six percent of healthy donor peripheral blood samples were positive by Q-PCR. In most of these samples, viral load was less than 2,000 EBV copies/ml of blood. In peripheral blood samples from two AIDS-related non-Hodgkin's lymphoma patients, elevated EBV loads (up to 120,000 copies/ml) were observed, which decreased upon therapy. In Burkitt's lymphoma patients, up to 4,592,000 EBV genome copies/ml of blood were detected. In conclusion, the EBNA-1-based Q-PCR assay provides a reproducible, accurate, and easy method for studying the relationship between EBV load and clinical parameters.

Published
1999

27. Decrease of HIV-1 RNA levels in lymphoid tissue and peripheral blood during treatment with ritonavir, lamivudine and zidovudine. Ritonavir/3TC/ZDV Study Group

Author

Notermans, D. W., Jurriaans, S., de Wolf, F., Foudraine, N. A., de Jong, J. J., Cavert, W., Schuwirth, C. M., Kauffmann, R. H., Meenhorst, P. L., McDade, H., Goodwin, C., Leonard, J. M., Goudsmit, J., Danner, S. A., and Other departments

Abstract

Triple combination treatment of HIV-1 infection using two reverse transcriptase inhibitors and a protease inhibitor can result in significant and sustained decreases in the quantity of viral RNA in peripheral blood. Lymphoid tissue, however, constitutes the major reservoir of HIV in infected patients. Study of the viral burden in these tissues has provided additional insight in the efficacy of antiretroviral treatment. Patients were randomized into two groups in order to study differences in the development of resistance to reverse transcriptase inhibitors. Group I started treatment with all three drugs simultaneously. Group II started with ritonavir monotherapy, aiming at initial reduction in virus production before the addition of lamivudine and zidovudine 3 weeks later. Changes in the amount of HIV in plasma and tonsillar lymphoid tissue during 24 weeks of treatment with ritonavir, lamivudine and zidovudine were studied by reverse transcriptase polymerase chain reaction. Thirty-three antiretroviral-naive HIV-infected patients were included for analysis. After 24 weeks, median CD4+ cell count increased by 152 x 10(6)/l and median plasma viral RNA levels decreased by at least 2.87 log10 copies/ml. In 88% of the patients remaining on treatment, plasma RNA levels were below the quantification limit of the assay used (mean, 2.4 log10 copies/ml). The lymphoid tissue viral burden, ranging from 9.16 to 8.52 log10 copies/g at baseline, was markedly reduced with at least 2.1 log10 copies/g by week 24 in the five patients analysed. Eight patients (24%) withdrew because of side-effects. In one patient in group II, ritonavir and lamivudine resistance-associated mutations developed. Treatment with this triple antiretroviral drug combination produced a durable and strong decrease of HIV-1 RNA burden in both plasma and lymphoid tissue

Published
1998

28. Evaluation of clinical pharmacist interventions on drug interactions in outpatient pharmaceutical HIV-care

Author

de Maat, M M R, de Boer, A, Koks, C H W, Mulder, J W, Meenhorst, P L, van Gorp, E C M, Mairuhu, A T A, Huitema, A D R, Beijnen, J H, de Maat, M M R, de Boer, A, Koks, C H W, Mulder, J W, Meenhorst, P L, van Gorp, E C M, Mairuhu, A T A, Huitema, A D R, and Beijnen, J H

Abstract

OBJECTIVE: To evaluate the usefulness of intervention in drug interactions of antiretroviral drugs with coadministered agents by a clinical pharmacist in outpatient HIV-treatment.METHODS: The study design included two intervention arms (A and B), which were both preceded by a control observation period. In arm A, a complete list of the currently used drugs, extracted from pharmacy records was provided to the treating physician. In arm B the same list was provided but with a notification when a drug interaction was present and an advice how to handle this. The infectious disease specialist obtained the information before the patient's visit to the outpatient clinic (time point 0). Three months prior (time point -3) and 3 months after (time point +3) the intervention, pharmacy records were also screened for drug interactions. The number of drug interactions (total and per patient) was determined at the three different time points (-3, 0, +3). In addition, drug interactions encountered at time points -3 and 0 were checked for their presence at time points 0 and +3, respectively, for both intervention arms.RESULTS: Arms A and B included 115 and 105 patients, respectively. Patient characteristics of both intervention arms were similar at time point 0. The number of interactions and the number of patients with interactions were similar in both intervention arms at time point 0. There were 42 and 40 potential drug interactions in 30 and 24 patients in arms A and B, respectively. The reduction in the number of interactions per patient over time and after intervention was small but significant, and was equal in both intervention arms. The advice of the clinical pharmacist had thus no additional value.CONCLUSION: Both interventions were effective in reducing the number of drug interactions per patient. The advice of a clinical pharmacist was, however, redundant in the studied setting.

Published
2004

29. Evaluation of clinical pharmacist interventions on drug interactions in outpatient pharmaceutical HIV-care

Author

Dep Farmaceutische wetenschappen, Sub Pharmacotherapy, Theoretical, Sub General Pharmaceutics, Sub Clinical Pharmacology, de Maat, M M R, de Boer, A, Koks, C H W, Mulder, J W, Meenhorst, P L, van Gorp, E C M, Mairuhu, A T A, Huitema, A D R, Beijnen, J H, Dep Farmaceutische wetenschappen, Sub Pharmacotherapy, Theoretical, Sub General Pharmaceutics, Sub Clinical Pharmacology, de Maat, M M R, de Boer, A, Koks, C H W, Mulder, J W, Meenhorst, P L, van Gorp, E C M, Mairuhu, A T A, Huitema, A D R, and Beijnen, J H

Published
2004

30. Effect of IFN-gamma on the proliferation of Toxoplasma gondii in monocytes and monocyte-derived macrophages from AIDS patients

Author

Delemarre, F G, Stevenhagen, A, Kroon, F P, van Eer, M Y, Meenhorst, P L, and van Furth, R

Subjects
Acquired Immunodeficiency Syndrome, AIDS-Related Opportunistic Infections, Macrophages, Hydrogen Peroxide, Monocytes, Recombinant Proteins, Interferon-gamma, parasitic diseases, Animals, Humans, Toxoplasma, Zidovudine, Cells, Cultured, Toxoplasmosis, Research Article
Abstract

This study was undertaken to determine whether the activity of monocytes and monocyte-derived macrophages (MDM) from acquired immune deficiency syndrome (AIDS) patients against Toxoplasma gondii is altered and whether this activity can be modulated by recombinant interferon-gamma (rIFN-gamma). Untreated and rIFN-gamma-treated monocytes or MDM from AIDS patients and from healthy controls were infected with T. gondii and the proliferation of these protozoa was determined. The H2O2 release by monocytes from AIDS patients and healthy controls was measured upon stimulation with phorbol myristate acetate (PMA) and formyl methionyl leucyl phenylalanine (FMLP). Monocytes from AIDS patients exhibited significantly lower toxoplasmastic activity compared to monocytes from healthy controls. The H2O2 release by monocytes from AIDS patients was also diminished. Incubation of monocytes from AIDS patients with rIFN-gamma for 2 days, but not 1 day, restored their toxoplasmastatic activity. The rate of proliferation of T. gondii was higher in MDM from AIDS patients than in MDM from healthy controls. Treatment of MDM from AIDS patients with rIFN-gamma for 1, 2 or 3 days resulted in partial inhibition of the proliferation of T. gondii. Collectively, these results demonstrate that the reduced toxoplasmastatic activity of monocytes and MDM from AIDS patients can be enhanced by in vitro treatment with rIFN-gamma, which supports the clinical use of rIFN-gamma for the treatment of opportunistic infections in these patients.

Published
1994

40. ITRACONAZOLE SOLUTION: SUMMARY OF PHARMACOKINETIC FEATURES AND REVIEW OF ACTIVITY IN THE TREATMENT OF FLUCONAZOLE-RESISTANT ORAL CANDIDOSIS IN HIV-INFECTED PERSONS

Author

KOKS, C. H. W., MEENHORST, P. L., BULT, A., and BEIJNEN, J. H.

Subjects
*PHARMACOKINETICS, *CANDIDIASIS treatment, *HIV-positive persons, *CYCLODEXTRINS
Abstract

The clinical pharmacology of itraconazole is presented in relation to its use in the treatment of fluconazole-resistant oropharyngeal candidosis. The oral solution is a new formulation of itraconazole in which itraconazole is solubilised with the use of cyclodextrin. This formulation has a higher bioavailability and leads to higher local concentrations in the oral cavity which are advantages over the solid capsule formulation. Literature, in which the use of itraconazole oral solution was described to treat fluconazole-resistant oral candidosis, is reviewed. In about 55% of the patients signs and symptoms of oral candidosis were resolved after treatment with itraconazole oral solution. Although all the reviewed studies lack data to objectively qualify all the included patients as having a fluconazole-resistant candidosis, the authors conclude, that based on the available information itraconazole oral solution 100 or 200 mg twice daily can be effective for fluconazole-resistant oropharyngeal candidosis (OPC) and should be considered prior to salvage therapy with intravenous amphotericin B. The use of itraconazole, however, requires careful monitoring of the patients co-medication for potential serious drug-drug interactions. [Copyright &y& Elsevier]

Published
2002
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41. Survival After Massive Ecstasy Overdose.

Author

Ramcharan, S., Meenhorst, P. L., Otten, J. M. M. B., Koks, C. H. W., de Boer, D., Maes, R. A. A., and Beijnen, J. H.

Subjects
*ECSTASY (Drug), *DRUG overdose, *METHAMPHETAMINE, *PSYCHIATRIC drugs, *DRUG abuse
Abstract

Describes a patient who had recovered from Ecstasy overdose. Effects of 3,4-methylenedioxymethampetamine (MDMA) on the user; Findings on the physical examination of the patient; Phases of MDMA actions to the user.

Published
1998
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43. Impaired phagocytosis of Staphylococcus aureus by granulocytes and monocytes of AIDS patients.

Author

Pos, O., Stevenhagen, A., Meenhorst, P. L., Kroon, F. P., and Van Furth, R.

Subjects
PHAGOCYTOSIS, IMMUNE response, ANTIGEN-antibody reactions, STAPHYLOCOCCUS aureus, STAPHYLOCOCCUS, MONOCYTES, AIDS patients
Abstract

In the present study the microbicidal activities of granulocytes and monocytes from AIDS patients (CDC group IV) were assessed and compared with those of healthy controls. The phagocytosis and intracellular killing of Staphylococcus aureus by patient and control cells were measured using a method in which the rate of intracellular killing can be assessed independently of the rate of phagocytosis. Both granulocytes and monocytes of AIDS patients showed a decreased phagocytosis of S. aureus in comparison to phagocytes of healthy individuals. The rates of intracellular killing of S. aureus by granulocytes and monocytes did not differ significantly between these patients with late- stage HIV infection and controls. [ABSTRACT FROM AUTHOR]

Published
1992

44. Detection of antibodies against Legionella pneumophila serogroups 1 to 6 and the Leiden-1 strain by micro ELISA and immunofluorescence assay.

Author

Herbrink, P, Meenhorst, P L, Groothuis, D G, Munckhof, H V, Bax, R, Meijer, C J, and Lindeman, J

Abstract

One hundred and seventy-five human sera were tested for the presence of type-specific antibodies against L pneumophila serogroups 1 to 6 and the Leiden-1 strain by means of an enzyme linked immunosorbent assay (ELISA) and compared with the results obtained by the indirect immunofluorescence assay (IFA). A high correlation (correlation coefficient 0.92) between both methods was found. No consistent pattern of IgG, IgA and IgM classes of antibody titres against L pneumophila were found. In the sera of 15 of 17 patients with a proven L pneumophila pneumonia, IgM class antibodies against L pneumophila could be detected. A "polyvalent" ELISA was developed which permits rapid routine screening of human sera for antibodies against L pneumophila serogroups 1 to 6 and the Leiden-1 strain. [ABSTRACT FROM PUBLISHER]

Published
1983

45. High Prevalence of Human Papillomavirus Infections in Urine Samples from Human Immunodeficiency Virus-Infected Men

Author

Smits, Paul H. M., Bakker, Remco, Jong, Eefje, Mulder, Jan Willem, Meenhorst, Pieter L., Kleter, Bernhard, van Doorn, Leen-Jan, and Quint, Wim G. V.

Abstract

ABSTRACTInfection with human immunodeficiency virus (HIV) and the resulting immunosuppression are associated with an increased risk for human papillomavirus (HPV) persistence and related malignancies. In the present study we investigated the prevalence of HPV in urine samples from 104 HIV-infected men with low CD4+cell counts (<100 per mm3) and 115 urine samples from HIV-negative men. A high prevalence of HPV DNA (39.4%) was found in the HIV patients. Most of the HPV types were high risk (81.4%), with HPV 52 as the most prevalent type (12.5%), followed by HPV 18 (6.7%), HPV 35 (5.8%), and HPV 70 (4.8%). Multiple HPV genotypes were observed in 17 (41%) of the 41 HPV- and HIV-positive men. In contrast, only 11 (9.6%) HPV DNA-positive cases were observed among the 115 HIV-uninfected men, and 3 (27.3%) contained multiple genotypes. Quantitative analyses indicated that the HPV viral load, as measured in urine samples, is significantly higher in HIV-positive men compared to HIV-negative men. In the present study we show that urine samples are useful for detecting HPV DNA, there is a high prevalence of HPV in HIV-positive men, and the HPV viral load is substantially higher in HIV-positive than in HIV-negative men. More studies are needed to evaluate the risk and natural development of HPV-related malignancies in HIV-positive men.

Published
2005
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46. The Plasma and Intracellular Steady-State Pharmacokinetics of Lopinavir/Ritonavir in HIV-1-Infected Patients

Author

Crommentuyn, Kristel ML, Mulder, Jan W, Mairuhu, Albert TA, van Gorp, Eric CM, Meenhorst, Pieter L, Huitema, Alwin DR, and Beijnen, Jos H

Abstract

Therapeutic drug monitoring of protease inhibitors (PIs) is usually performed on plasma samples although their antiretroviral effect takes place inside cells. Little is known, however, about the intracellular accumulation and related plasma pharmacokinetics of PIs such as lopinavir/ritonavir (LPV/RTV). Therefore, we studied the plasma and intracellular (cell-associated) steady-state pharmacokinetics of this PI combination in a dosage of 400/100 mg twice daily in a non-randomized cohort of HIV-1-infected individuals. Plasma (0–12 h) and peripheral blood mononuclear cell (PBMC; 0–8 h) samples were drawn during a 12-h dosing interval in 11 subjects.The plasma concentrations versus time curves of LPV and RTV were characterized by an irregular absorption phase showing double-peaks (Cmax) in most subjects and single-peaks in the remaining patients between 1 and 3 h after drug intake. Pre-dose concentrations of both agents in plasma were significantly higher than the concentrations at the end of the dosing interval indicating the presence of a circadian rhythm in their pharmacokinetics. The course of the intracellular concentrations versus time curves appeared to be similar to the plasma concentration curves, with the highest intracellular concentration measured 3 h after drug intake. The intracellular RTV concentrations were higher than reported in vitroEC50values and might therefore contribute to the antiretroviral effect of LPV/RTV. The median intracellular-to-plasma concentration ratios (interquartile range) were 1.18 (0.74–2.06) and 4.59 (3.20–7.70) for LPV and RTV, respectively.In conclusion, both LPV and RTV accumulate to potential therapeutic concentrations in PBMCs. Irregular absorption and circadian plasma clearance patterns were observed for the PI combination LPV/RTV.

Published
2004
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47. Subtherapeutic Antiretroviral Plasma Concentrations in Routine Clinical Outpatient HIV Care

Author

Maat, Monique M. R. de, Huitema, Alwin D. R., Mulder, Jan W., Meenhorst, Pieter L., Gorp, Eric C. M. van, Mairuhu, Albert T. A., and Beijnen, Jos H.

Abstract

The objective of this study was to evaluate plasma concentrations of nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) within several dosing schemes in a cohort of HIV-infected patients in routine clinical practice and to find possible explanations for subtherapeutic plasma concentrations. Patients were included if a PI or NNRTI was part of their antiretroviral regimen, at least one plasma concentration was obtained, and a complete medication overview from community pharmacy records was available. The study period was from January 1998 to September 2001. Each plasma concentration was related to median plasma concentrations of a pharmacokinetic reference curve, yielding a concentration ratio (CR). A cutoff CR was defined for each antiretroviral drug per specific regimen, discriminating between ≥therapeutic and subtherapeutic concentrations. For the patients with subtherapeutic concentrations, it was sorted out whether drug interactions, adverse events and self-reported symptoms, or nonadherence could be the cause of the lower than expected plasma concentration. Ninety-seven HIV-infected patients fulfilled the criteria. During the defined period, 1145 plasma concentrations were available (median, 11; interquartile range, 8–14). Three hundred fourteen (27.4) plasma concentrations were classified subtherapeutic. Drug interactions (2; 0.6), adverse events and self-reported symptoms (67; 21.3), and nonadherence (14; 4.5) could only partly explain the subtherapeutic drug levels. Consequently, a large number of the subtherapeutic plasma concentrations (73.6) remained inexplicable. A high number of subtherapeutic plasma concentrations were observed. No clear causes were found; thus, corrective measures will be difficult to employ. Therefore, therapeutic drug monitoring (TDM) must maintain its crucial place in routine clinical care to be able to identify patients who need extra attention so that therapeutic plasma concentrations are achieved.

Published
2003

48. Discrepancies between Medical and Pharmacy Records for Patients on Anti-HIV Drugs

Author

de Maat, Monique MR, Frankfort, Suzanne V, Mathôt, Ron AA, Mulder, Jan W, Meenhorst, Pieter L, van Gorp, Eric CM, Koks, Cornelis HW, Hoetelmans, Richard MW, de Boer, Anthonius, and Beijnen, Jos H

Abstract

OBJECTIVE: To compare and evaluate drug notations in outpatient medical records and in pharmacy records in a cohort of HIV-1–infected patients treated with antiretroviral drugs.METHODS: Data on 103 patients were obtained from January 1, 1998, through December 31, 1999, by medical chart review and collection of pharmacy records. Two analyses were performed. First, antiretroviral drugs and comedication in the pharmacy records were documented and compared with their appearance in the outpatient medical records. Second, a detailed comparison was performed at 5 time points during the study period for the antiretroviral drugs. Generic name, formulation, strength, and frequency of dosing as registered in the outpatient medical records were compared with those registered in the pharmacy records.RESULTS: Total drug dispensation was 1607 (366 and 1241 antiretroviral drugs and comedication, respectively). The first screening resulted in a total discrepancy of 55.1% (n = 885), of which 97.1% (n = 859) was attributed to the comedication and 2.9% (n = 26) to the antiretroviral drugs. The discrepancy for the antiretroviral drugs at the specific time points ranged from 5.1% to 12.6% when the generic name only was used, and from 7.1% to 17% when formulation, strength, and frequency of dosing were also taken into account.CONCLUSIONS: The observed discrepancy between outpatient medical records and pharmacy records mainly concerns the comedication. For the antiretroviral drugs fewer, but still substantial, discrepancies were observed. These results indicate that full exchange of information concerning drug use in this population between general practitioners and specialists (infectious disease) is lacking.

Published
2002
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50. Limited Sampling Strategies for the Estimation of the Systemic Exposure to the HIV-1 Nonnucleoside Reverse Transcriptase Inhibitor Nevirapine

Author

Veldkamp, Agnes I., Heeswijk, Rolf P. G. van, Mulder, Jan W., Meenhorst, Pieter L., Hoetelmans, Richard M. W., Lange, Joep M. A., and Beijnen, Jos H.

Abstract

The objective of this study was to develop and validate a limited sampling strategy (LSS) that allows accurate and precise estimation of the area under the plasma concentration versus time curve (AUC) of nevirapine, when used in the licensed dosage of 200 mg twice daily. Because nevirapine has a long plasma elimination half-life and the plasma concentration shows little variation within the 12-hour dosing interval, the authors also wanted to explore whether a time frame exists for which a single-sample LSS can be applied. Twenty HIV-1-infected individuals receiving steady-state treatment with nevirapine (200 mg twice daily) were enrolled. For the development of the LSS, 10 patients were randomly selected from the study population (index set). The pharmacokinetic results from the other 10 patients (validation set) were used for prospective validation of the proposed LSS. Blood samples were obtained before and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, and 12 hours after ingestion. The relationship between the nevirapine concentration at each of the designated time points and the AUC 12hwas evaluated by univariate and multivariate linear regression analysis. At each of the sampling times, a strong correlation was observed between the nevirapine concentration and the corresponding AUC 12h(r> 0.97). This allows for a single-sample LSS, using any time point during the dosing interval. When a single equation is preferred, the concentration of nevirapine in a random sample drawn 2 to 4 hours after ingestion of nevirapine (C 2–4h; in g/mL) can be used for accurate estimation of the AUC 12h(in h · g/mL) by using the equation AUC 12h(h · g/mL) 11.699 (h) × C 2–4h(g/mL) - 4.381 (h · g/mL). Validation of this equation resulted in a predicted AUC 12hthat was nonbiased and very precise. These data show that the nevirapine concentration at each time point during the dosing interval can be used for accurate estimation of the AUC 12h. Even more practical, a sample obtained at any time between 2 and 4 hours after ingestion of nevirapine can be used. The authors therefore conclude that less intensive sampling (i.e., a single sample) can readily be used to assess the AUC 12hof nevirapine when used in a dosage of 200 mg twice daily.

Published
2001

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