Plasma pharmacokinetics of once-daily abacavir- and lamivudine-containing regimens and week 96 efficacy in HIV-infected Thai children

• Asıl Yazarlar: Torsak Bunupuradah (Yazar), Passorn Punyahotra (Yazar), Tim R. Cressey (Yazar), Amornrat Srimuan (Yazar), Narukjaporn Thammajaruk (Yazar), Jiratchaya Sophonphan (Yazar), Chulalak Sriheara (Yazar), David M. Burger (Yazar), Thanyawee Puthanakit (Yazar), Jintanat Ananworanich (Yazar)
• Materyal Türü: Kitap
• Baskı/Yayın Bilgisi: Elsevier, 2015-07-01T00:00:00Z.
• Konular: article
• Online Erişim: Connect to this object online.
• Notes: 2055-6640; 10.1016/S2055-6640(20)30503-3
• Keywords: abacavir; lamivudine; pharmacokinetics; once-daily; HIV-infected children; Microbiology; QR1-502; Public aspects of medicine; RA1-1270
• Source: Journal of Virus Eradication, Vol 1, Iss 3, Pp 185-191 (2015)

Background: Abacavir and lamivudine are approved for once-daily use in HIV-infected adults Limited pharmacokinetic (PK) data for abacavir and lamivudine in children are available. Methods: A crossover study to compare PK of once- versus twice-daily abacavir and lamivudine was conducted in virologically suppressed HIV-infected Thai children aged <18years, with bodyweight of at least 14 kg, HIV RNA <50 copies/mL and HLA-B*5701 negative. Abacavir and lamivudine daily doses by bodyweight were 300 and 150 mg for 14-<20 kg, 450 and 300 mg for 20-<25 kg, and 600 and 300 mg for ≥25 kg, respectively. Originator abacavir and lamivudine scored tablets were administered. Intensive PK sampling was performed after 14 days of each dose. PK parameters were determined using non-compartmental analysis. Results: Thirty children (57% male) were enrolled, 10 per weight band. Median (IQR) age was 8.8 (6.6-11.3) years and bodyweight was 21.9 (19.2-30.6) kg. The geometric means (GM) AUC0-24 of once- and twice-daily abacavir were 14.43 and 10.65 mg.h/L, respectively. The geometric mean ratio (GMR) of AUC0-24 for once- versus twice-daily abacavir dosing was 1.36 [90% confidence interval (CI) 1.11-1.66]. The GM AUC0-24 of once- and twice-daily lamivudine were 17.70 and 18.11 mg.h/L, respectively. The GMR of AUC0-24 for once- versus twice-daily lamivudine dosing was 0.98 (90% CI 0.84-1.14). At 96 weeks, 90% had HIV RNA <50 copies/mL and there were no serious adverse events. Conclusion: Abacavir exposure was greater with once-daily dosing, while lamivudine once- and twice-daily exposures were bioequivalent. Once-daily abacavir and lamivudine using weight-band dosing is a treatment option for children.