Pharmacokinetics and Safety of a New Paediatric Fixed-Dose Combination of Zidovudine/Lamivudine/Nevirapine in HIV-Infected Children
| Autor: | Petronella Muresan, Chaiwat Ngampiyaskul, Edmund V. Capparelli, Mary E. Smith, Ram Yogev, Virat Sirisanthana, Kenneth McIntosh, Kulkanya Chokephaibulkit, Chanin Limwongse, Orasri Wittawatmongkol, Bill Kabat, Tim R. Cressey, Mari Pat Toye, Achara Eksaengsri, Suchat Hongsiriwon, Linda Aurpibul |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Pediatrics medicine.medical_specialty Nevirapine Drug-Related Side Effects and Adverse Reactions Anti-HIV Agents Fixed-dose combination Biological Availability HIV Infections Pharmacology Article Drug Administration Schedule Zidovudine Pharmacokinetics Hiv infected Humans Medicine Drug Dosage Calculations Pharmacology (medical) Child Cumulative toxicity business.industry Zidovudine lamivudine nevirapine Body Weight HIV Infant Lamivudine Oxidoreductases N-Demethylating Cytochrome P-450 CYP2B6 Drug Combinations Infectious Diseases Area Under Curve Child Preschool Reverse Transcriptase Inhibitors Drug Therapy Combination Female Aryl Hydrocarbon Hydroxylases business Tablets medicine.drug |
| Zdroj: | Antiviral Therapy. 16:1287-1295 |
| ISSN: | 2040-2058 1359-6535 |
| DOI: | 10.3851/imp1931 |
| Popis: | Background Alternatives to the available stavudine-containing paediatric fixed-dose combination (FDC) tablets are rapidly needed due to concerns regarding the cumulative toxicity of long-term stavudine exposure. We report the bioavailability and short-term safety of a novel paediatric FDC tablet of zidovudine (ZDV)/lamivudine (3TC)/nevirapine (NVP; 30/15/28 mg) in HIV-infected children. Methods In this Phase I/II open-label pharmacokinetic study, 42 children weighing 6–30 kg treated with NVP-based HAART for ≥4 weeks were randomized to receive the FDC tablets (GPO-VIR Z30) or the liquid formulations. Dosing was weight-based. Intensive 12-h blood sampling was performed after 2 weeks; subjects then crossed-over to the alternate formulation at equal doses and sampling repeated 2 weeks later. Pharmacokinetic parameters were determined by non-compartmental analysis. Buccal-swab samples were collected for cytochrome P450 ( CYP)2B6 polymorphism analysis. Results With the FDC tablet, the geometric mean (90% CI) area under the curve (AUC) for ZDV, 3TC and NVP was 1.58 (1.49-1.68), 7.78 (7.38-8.19) and 68.88 (62.13-76.36) μg•h/ml, respectively. Rules for NVP therapeutic inadequacy were defined a priori, and despite lower NVP exposure with the tablet ( P Conclusions Disparities in drug exposure between formulations were observed; however, the FDC tablet delivered therapeutically adequate exposures of each drug and could well play an important role in simplifying antiretroviral treatment for children. |
| Databáze: | OpenAIRE |
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