Hirt D., Bardin C., Diagbouga S., Nacro B., Hien H., Zoure E., Rouet F., Ouiminga A., Urien S., Foulongne V., Van de Perre P., Tréluyer J. M., Msellati Philippe. (2009). Didanosine population pharmacokinetics in West African human immunodeficiency virus-infected children administered once-daily tablets in relation to efficacy after one year of treatment. Antimicrobial Agents and Chemotherapy, 53 (10), 4399-4406. ISSN 0066-4804.
Titre du document
Didanosine population pharmacokinetics in West African human immunodeficiency virus-infected children administered once-daily tablets in relation to efficacy after one year of treatment
Année de publication
2009
Auteurs
Hirt D., Bardin C., Diagbouga S., Nacro B., Hien H., Zoure E., Rouet F., Ouiminga A., Urien S., Foulongne V., Van de Perre P., Tréluyer J. M., Msellati Philippe
Source
Antimicrobial Agents and Chemotherapy, 2009,
53 (10), 4399-4406 ISSN 0066-4804
Our objective was to study didanosine pharmacokinetics in children after the administration of tablets, the only formulation available in Burkina Faso for which data are missing, and to establish relationships between doses, plasma drug concentrations, and treatment effects (efficacy/toxicity). Didanosine concentrations were measured for 40 children after 2 weeks and for 9 children after 2 to 5 months of treatment with a didanosine-lamivudine-efavirenz combination. A population pharmacokinetic model was developed with NONMEM. The link between the maximal concentration of the drug in plasma (C-max), the area under the concentration-time curve (AUC), and the decrease in human immunodeficiency virus (HIV) type 1 RNA levels after 12 months of treatment was evaluated. The threshold AUC that improved efficacy was determined by the use of a Wilcoxon test for HIV RNA, and an optimized dosing schedule was simulated. Didanosine pharmacokinetics was best described by a one-compartment model with first-order absorption and elimination. The apparent clearance and volume of distribution were higher for tablets, probably due to a lower bioavailability with tablets than with pediatric powder. The decrease in the viral load after 12 months of treatment was significantly correlated with the didanosine AUC and C-max (P <= 0.02) during the first weeks of treatment. An AUC of > 0.60 mg/liter . h was significantly linked to a greater decrease in the viral load (a decrease of 3 log(10) versus 2.4 log(10) copies/ml; P = 0.03) than that with a lower AUC. A didanosine dose of 360 mg/m(2) administered as tablets should be a more appropriate dose than 240 mg/m(2) to improve efficacy for these children. However, data on adverse events with this dosage are missing.
Plan de classement
Santé : généralités [050]
;
Entomologie médicale / Parasitologie / Virologie [052]
Description Géographique
BURKINA FASO
Localisation
Fonds IRD [F B010089806]
Identifiant IRD
PAR00004147
