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Your search keyword '"Kiechel, J.R."' showing total 13 results
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13 results on '"Kiechel, J.R."'

1. Lopinavir/ritonavir plus lamivudine and abacavir or zidovudine dose ratios for paediatric fixed-dose combinations

Author

Bouazza, N., Foissac, F., Fauchet, F., Burger, D.M., Kiechel, J.R., Treluyer, J.M., Capparelli, E.V., Lallemant, M., Urien, S., Bouazza, N., Foissac, F., Fauchet, F., Burger, D.M., Kiechel, J.R., Treluyer, J.M., Capparelli, E.V., Lallemant, M., and Urien, S.

Abstract

Item does not contain fulltext, BACKGROUND: Lopinavir/ritonavir (LPV/r) is available in a liquid formulation that is far from ideal for treatment of children in resource-poor settings. Flexible, low-cost, solid, oral fixed-dose combinations (FDC) of LPV/r with nucleoside reverse transcriptase inhibitors (LPV/r/abacavir [ABC]/lamivudine [3TC] and LPV/r/zidovudine [ZDV]/3TC) are needed to improve both management and adherence of children. This work aimed to develop appropriate drug ratios and dosing for each FDC. METHODS: Data from 25 combined datasets included therapeutic drug monitoring and clinical studies from IMPAACT and PENTA. Population pharmacokinetic analyses were performed using Monolix. Monte-Carlo simulations of WHO and FDA dosing recommendations were performed to assess their ability to provide optimal exposure in children weighing 4 to 25 kg based on consensus plasma targets. The LPV/r:3TC:ZDV(ABC) dose ratios were 2.67:1:2(2), respectively. RESULTS: Using WHO dosage, LPV efficacy target was reached in all weight bands. Given the recommended drug ratios, the dosage for the 4-5.9 kg weight band (LPV/ZDV: 120/90 mg twice daily [bid]) showed more than 20% of subjects had ZDV levels at high risk of neutropenia. Reducing the LPV/ZDV dose to 80/60 mg bid decreased frequency of high ZDV concentrations but retained the LPV efficacy criteria. CONCLUSIONS: This defined a flexible and simple FDC containing 40 mg LPV, 10 mg ritonavir, 15 mg 3TC and 30 mg ABC or ZDV. According to the weight bands defined by WHO, 4-5.9 kg, 6-9.9 kg, 10-13.9 kg, 14-19.9 kg, 20-24.9 kg, therapeutic doses would be 2, 3, 4, 5 or 6 individual units administered by oral route bid.

Published
2015

13. Artemether-lumefantrine treatment of uncomplicated Plasmodium falciparum malaria: a systematic review and meta-analysis of day 7 lumefantrine concentrations and therapeutic response using individual patient data

Author

Nicholas J. White, Jullien, Andreas Mårtensson, Carol Hopkins Sibley, Steffen Borrmann, Gilbert Lefèvre, Michèle van Vugt, Karen I. Barnes, François Nosten, Christian Nsanzabana, Lars Rombo, Rose McGready, Kamal Hamed, Blaise Genton, Harin Karunajeewa, Francesca T. Aweeka, Philippe J Guerin, Liusheng Huang, Birgit Schramm, Pascal Ringwald, Tme Davis, Johan Ursing, Sunil Parikh, Eva Maria Hodel, Mey Bouth Denis, Prabin Dahal, C Moreira, Mayfong Mayxay, Ric N. Price, Kiechel, Kasia Stepniewska, Paul N. Newton, Lesley Workman, Quique Bassat, Poul-Erik Kofoed, Billy Ngasala, Philippe Deloron, Elizabeth A. Ashley, Niklas Lindegardh, Jean-François Faucher, Kevin Marsh, Abdoulaye Djimde, WorldWide Antimalarial Resistance Network (WWARN) Lumefantrine PK/PD Study Group, Ashley, E.A., Aweeka, F., Barnes, K.I., Bassat, Q., Borrmann, S., Dahal, P., Davis, T.M., Deloron, P., Denis, M.B., Djimde, A.A., Faucher, J.F., Genton, B., Guérin, P.J., Hamed, K., Hodel, E.M., Huang, L., Jullien, V., Karunajeewa, H.A., Kiechel, J.R., Kofoed, P.E., Lefèvre, G., Lindegardh, N., Marsh, K., Mårtensson, A., Mayxay, M., McGready, R., Moreira, C., Newton, P.N., Ngasala, B.E., Nosten, F., Nsanzabana, C., Parikh, S., Piola, P., Price, R.N., Ringwald, P., Rombo, L., Schramm, B., Sibley, C.H., Stepniewska, K., Tarning, J., Ursing, J., Van Vugt, M., White, N.J., and Workman, L.J.

Subjects
Artemether/lumefantrine, Baseline parasitemia, Drug resistance, Parasitemia, Pharmacology, Artemisinins/therapeutic use, chemistry.chemical_compound, 0302 clinical medicine, Recurrence, 030212 general & internal medicine, Treatment Failure, Malaria, Falciparum, Artemether-lumefantrine, Medicine(all), 0303 health sciences, biology, Malaria, Falciparum/drug therapy, Fluorenes/therapeutic use, Antimalarials/administration & dosage, Antimalarials/therapeutic use, Dose-Response Relationship, Drug, Drug Therapy, Combination, Ethanolamines/therapeutic use, Humans, General Medicine, Artemisinins, 3. Good health, Medicaments antipalúdics, Ethanolamines, Meta-analysis, Uncomplicated Plasmodium falciparum malaria, Artemether, Erratum, Early parasitological response, medicine.drug, Research Article, medicine.medical_specialty, Plasmodium falciparum, Pharmacokinetic, Malària, Lumefantrine, Online bibliographic searching, 03 medical and health sciences, Antimalarials, Internal medicine, medicine, Dosing, Cerca documental en línia, 030304 developmental biology, Fluorenes, Pharmacodynamic, business.industry, Malnutrition, medicine.disease, biology.organism_classification, Day 7 lumefantrine concentration, Malaria, chemistry, business
Abstract

BACKGROUND: Achieving adequate antimalarial drug exposure is essential for curing malaria. Day 7 blood or plasma lumefantrine concentrations provide a simple measure of drug exposure that correlates well with artemether-lumefantrine efficacy. However, the 'therapeutic' day 7 lumefantrine concentration threshold needs to be defined better, particularly for important patient and parasite sub-populations. METHODS: The WorldWide Antimalarial Resistance Network (WWARN) conducted a large pooled analysis of individual pharmacokinetic-pharmacodynamic data from patients treated with artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria, to define therapeutic day 7 lumefantrine concentrations and identify patient factors that substantially alter these concentrations. A systematic review of PubMed, Embase, Google Scholar, ClinicalTrials.gov and conference proceedings identified all relevant studies. Risk of bias in individual studies was evaluated based on study design, methodology and missing data. RESULTS: Of 31 studies identified through a systematic review, 26 studies were shared with WWARN and 21 studies with 2,787 patients were included. Recrudescence was associated with low day 7 lumefantrine concentrations (HR 1.59 (95% CI 1.36 to 1.85) per halving of day 7 concentrations) and high baseline parasitemia (HR 1.87 (95% CI 1.22 to 2.87) per 10-fold increase). Adjusted for mg/kg dose, day 7 concentrations were lowest in very young children (/=200 ng/ml were associated with >98% cure rates (if parasitemia /=200 ng/ml and high cure rates in most uncomplicated malaria patients. Three groups are at increased risk of treatment failure: very young children (particularly those underweight-for-age); patients with high parasitemias; and patients in very low transmission intensity areas with emerging parasite resistance. In these groups, adherence and treatment response should be monitored closely. Higher, more frequent, or prolonged dosage regimens should now be evaluated in very young children, particularly if malnourished, and in patients with hyperparasitemia.

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