Search

Your search keyword '"Siccardi, Marco"' showing total 665 results
Start Over Author "Siccardi, Marco"
665 results on '"Siccardi, Marco"'

53. Impact of body weight on virological and immunological responses to efavirenz-containing regimens in HIV-infected, treatment-naive adults

Author

Marzolini, Catia, Sabin, Caroline, Raffi, François, Siccardi, Marco, Mussini, Cristina, Launay, Odile, Burger, David, Roca, Bernardino, Fehr, Jan, Bonora, Stefano, Mocroft, Amanda, Obel, Niels, Dauchy, Frederic-Antoine, Zangerle, Robert, Gogos, Charalambos, Gianotti, Nicola, Ammassari, Adriana, Torti, Carlo, Ghosn, Jade, Chêne, Genevieve, Grarup, Jesper, and Battegay, Manuel

Published
2015
Full Text
View/download PDF

61. LONG-ACTING DRUGS AND FORMULATIONS FOR THE TREATMENT AND PREVENTION OF HIV

Author

Flexner, Charles, Owen, Andrew, Siccardi, Marco, and Swindells, Susan

Subjects
Canada, Drug Combinations, Drug Delivery Systems, Deoxyadenosines, Anti-HIV Agents, Pyridones, Delayed-Action Preparations, Rilpivirine, HIV-1, Humans, HIV Infections, HIV Antibodies, Article
Abstract

Long acting and extended-release formulations represent one of the most important approaches to improving the treatment and prevention of chronic HIV infection. Long acting small molecules and monoclonal antibodies have demonstrated potent anti-HIV activity in early and late stage clinical trials. Strategies to manage toxicities and falling drug concentrations after missed doses, as well as primary and secondary resistance to current drugs and monoclonal antibodies are important considerations. Long-acting injectable nanoformulations of the integrase inhibitor carbotegravir and the nonnucleoside reverse transcriptase inhibitor rilpivirine were safe, well tolerated, and efficacious in large randomized Phase 3 studies. Regulatory approval for this 2-drug combination for HIV maintenance therapy was granted in Canada in 2020 and is expected in the U.S. during 2021. 4′-ethynyl-2-fluoro-2′-deoxyadenosine (islatravir) is a novel nucleoside reverse transcriptase inhibitor in clinical development as a long acting oral drug and as a long-acting subcutaneous polymer implant. GS-6207 is a novel HIV capsid inhibitor that is injected subcutaneously every 3 months. Broadly neutralizing monoclonal antibodies have potent antiviral activity in early human trials; however, there is substantial baseline resistance, and rapid development of resistance to these antibodies if used as monotherapy. Limitations of these antiretroviral approaches include the management of toxicities, and prevention of drug resistance when these drugs are discontinued and drug concentrations are slowly reduced over time. These approaches appear to be especially attractive for patients complaining of pill fatigue, and for those experiencing HIV-associated stigma. As these formulations are shown to be safe, well-tolerated, and economical, they are likely to gain broader appeal.

Published
2020

69. Association of a single-nucleotide polymorphism in the pregnane X receptor (PXR 63396C(right arrow)T) with reduced concentrations of unboosted atazanavir

Author

Siccardi, Marco, D'Avolio, Antonio, Baietto, Lorena, Gibbons, Sara, Sciandra, Mauro, Colucci, Daniela, Bonora, Stefano, Khoo, Saye, Back, David J., Perri, Giovanni Di, and Owen, Andrew

Subjects
Atazanavir -- Dosage and administration, Atazanavir -- Physiological aspects, Genetic polymorphisms -- Research, Blood plasma -- Research, Blood plasma -- Physiological aspects, Genetic screening -- Usage, Health, Health care industry
Published
2008

70. Predicting pharmacokinetics of a tenofovir alafenamide subcutaneous implant using PBPK modelling

Author

Rajoli, Rajith KR, Demkovich, Zach R, Flexner, Charles, Owen, Andrew, and Siccardi, Marco

Abstract

Background and Objectives: Long-acting (LA) administration using a subcutaneous (SC) implant presents opportunities to simplify administration of antiretroviral drugs, improve pharmacological (PK) profile and overcome sub-optimal adherence associated with daily oral formulations. Tenofovir alafenamide (TAF) is a highly potent nucleoside reverse transcriptase inhibitor (NRTI) and an attractive agent for LA delivery, with a high potency and long intracellular half-life. The aim of this study was to predict minimum TAF doses required to achieve concentrations effective for HIV pre-exposure prophylaxis (PrEP). Daily drug-release requirements were then ascertained by averaging across the dosing interval.Methods: A TAF PBPK model was developed and partially qualified against available oral single- and multiple-dose pharmacokinetics. The models were assumed to be qualified when simulated values were within 2-fold of observed mean. TAF SC implants were simulated in five hundred individuals reporting predicted TAF plasma, tenofovir (TFV) plasma concentrations for various release rates. Intracellular TFV diphosphate (TFV-DP) concentrations were also simulated in peripheral blood cells, cervical and rectal tissues. The minimum dose predicted to achieve intracellular TFV-DP levels above target concentration of 48 fmol/106 cells for a month was identified.Results: TAF, TFV and TFV-DP concentrations for release rates between 1.0 and 1.6 mg/day were simulated. The PBPK model indicated a minimum release of 1.4 mg/day TAF is necessary to achieve TFV-DP concentrations above the identified target in PBMCs. TFV-DP cervical and rectal tissue concentration were predicted to be between 1.5 - 2.0 fmol/106 cells and 0.9 - 1.1 fmol/106 cells respectively for release rates between 1.3 - 1.6 mg/day.Discussion: These simulations provide target minimum doses for LA TAF PrEP in humans. Based on the generated results, multiple implants delivering a total of 1.4 mg/day of TAF subcutaneously could provide protections levels for approximately 6-months to 1 year. This modelling may inform future design of SC implants to mitigate adherence-issues for effective PrEP applications.

Published
2020

73. Recommendations for Dosing of Repurposed COVID-19 Medications in Patients with Renal and Hepatic Impairment

Author

Marra, Fiona, primary, Smolders, Elise J., additional, El-Sherif, Omar, additional, Boyle, Alison, additional, Davidson, Katherine, additional, Sommerville, Andrew J., additional, Marzolini, Catia, additional, Siccardi, Marco, additional, Burger, David, additional, Gibbons, Sara, additional, Khoo, Saye, additional, and Back, David, additional

Published
2020
Full Text
View/download PDF

79. Physiologically based pharmacokinetic modeling for dose optimization of quinine–phenobarbital coadministration in patients with cerebral malaria.

Author

Sae‐heng, Teerachat, Rajoli, Rajith Kumar Reddy, Siccardi, Marco, Karbwang, Juntra, and Na‐Bangchang, Kesara

Subjects
CEREBRAL malaria, ACUTE kidney failure, MALARIA, CYTOCHROME P-450, PHARMACOKINETICS, CONTINUOUS groups, CYTOCHROME P-450 CYP2C19
Abstract

Patients with cerebral malaria with polymorphic Cytochrome P450 2C19 (CYP2C19) genotypes who receive concurrent treatment with quinine are at risk of inadequate or toxic therapeutic drug concentrations due to metabolic drug interactions. The study aimed to predict the potential dose regimens of quinine when coadministered with phenobarbital in adult patients with cerebral malaria and complications (e.g., lactic acidosis and acute renal failure) and concurrent with seizures and acute renal failure who carry wild‐type and polymorphic CYP2C19. The whole‐body physiologically based pharmacokinetic (PBPK) models for quinine, phenobarbital, and quinine–phenobarbital coadministration were constructed based on the previously published information using Simbiology®. Four published articles were used for model validation. A total of 100 virtual patients were simulated based on the 14‐day and 3‐day courses of treatment. using the drug–drug interaction approach. The predicted results were within 15% of the observed values. Standard phenobarbital dose, when administered with quinine, is suitable for all groups with single or continuous seizures regardless of CYP2C19 genotype, renal failure, and lactic acidosis. Dose adjustment based on area under the curve ratio provided inappropriate quinine concentrations. The recommended dose of quinine when coadministered with phenobarbital based on the PBPK model for all groups is a loading dose of 2000 mg intravenous (i.v.) infusion rate 250 mg/h followed by 1200 mg i.v. rate 150 mg/h. The developed PBPK models are credible for further simulations. Because the predicted quinine doses in all groups were similar regardless of the CYP2C19 genotype, genotyping may not be required. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

83. Ribavirin pharmacokinetics and interleukin 28B plus cytochrome P450 27B1 single-nucleotide polymorphisms as predictors of response to pegylated interferon/ribavirin treatment in patients infected with hepatitis C virus genotype 1/4

Author

DʼAvolio, Antonio, Ciancio, Alessia, Siccardi, Marco, Baietto, Lorena, Simiele, Marco, Cariti, Giuseppe, Calcagno, Andrea, Smedile, Antonina, Cusato, Jessica, Bonora, Stefano, Rizzetto, Mario, and Di Perri, Giovanni

Published
2011
Full Text
View/download PDF

84. Cytochrome P450 2B6 (CYP2B6) and constitutive androstane receptor (CAR) polymorphisms are associated with early discontinuation of efavirenz-containing regimens

Author

Wyen, Christoph, Hendra, Heidy, Siccardi, Marco, Platten, Martin, Jaeger, Hans, Harrer, Thomas, Esser, Stefan, Bogner, Johannes R., Brockmeyer, Norbert H., Bieniek, Bernhard, Rockstroh, Juergen, Hoffmann, Christian, Stoehr, Albrecht, Michalik, Claudia, Dlugay, Verena, Jetter, Alexander, Knechten, Heribert, Klinker, Hartwig, Skaletz-Rorowski, Adriane, Fätkenheuer, Gerd, Egan, Deirdre, Back, David J., Owen, Andrew, Dupke, Stephan, Carganico, Andreas, Baumgarten, Axel, Koeppe, Siegfried, Kreckel, Peter, Lauenroth-Mai, Elke, Schlote, Frank, Schuler, Christoph, Freiwald, Matthias, Rausch, Michael, Gölz, Jörg, Moll, Arend, Zeitz, Martin, Brockmeyer, Norbert, Hower, Martin, Reuter, Stefan, Harrer, Thomas, Esser, Stefan, Staszewski, Schlomo, Plettenberg, Andreas, Fenske, Stefan, Buhk, Thomas, Stellbrink, Hans-Jürgen, Schmidt, Reinhold, Kuhlmann, Birger, Mosthaf, Franz, Rieke, Ansgar, Scholten, Stefan, Jaeger, Hans, Jaegel-Guedes, Eva, Volkert, Ramona, Becker, Werner, Hartl, Helmut, Mutz, Antonius, Ulmer, Albrecht, Frietsch, Bernhard, and Müller, Markus

Published
2011
Full Text
View/download PDF

95. Ribavirin pharmacokinetics and interleukin 28B plus cytochrome P450 27B1 single-nucleotide polymorphisms as predictors of response to pegylated interferon/ribavirin treatment in patients infected with hepatitis C virus genotype 1/4

Author

DʼAvolio, Antonio, Ciancio, Alessia, Siccardi, Marco, Baietto, Lorena, Simiele, Marco, Cariti, Giuseppe, Calcagno, Andrea, Smedile, Antonina, Cusato, Jessica, Bonora, Stefano, Rizzetto, Mario, and Di Perri, Giovanni

Published
2010
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results