Background: Abacavir and lamivudine are approved for once-daily use in HIV-infected adults. Limited pharmacokinetic\n(PK) data for abacavir and lamivudine in children are available.\nMethods: A crossover study to compare PK of once- versus twice-daily abacavir and lamivudine was conducted in\nvirologically suppressed HIV-infected Thai children aged <18years, with bodyweight of at least 14 kg, HIV RNA\n<50 copies/mL and HLA-B*5701 negative. Abacavir and lamivudine daily doses by bodyweight were 300 and 150 mg for\n14ââ?¬â??<20 kg, 450 and 300 mg for 20ââ?¬â??<25 kg, and 600 and 300 mg for ââ?°Â¥25 kg, respectively. Originator abacavir and\nlamivudine scored tablets were administered. Intensive PK sampling was performed after 14 days of each dose. PK\nparameters were determined using non-compartmental analysis.\nResults: Thirty children (57% male) were enrolled, 10 per weight band. Median (IQR) age was 8.8 (6.6ââ?¬â??11.3) years and\nbodyweight was 21.9 (19.2ââ?¬â??30.6) kg. The geometric means (GM) AUC0ââ?¬â??24 of once- and twice-daily abacavir were 14.43\nand 10.65 mg.h/L, respectively. The geometric mean ratio (GMR) of AUC0ââ?¬â??24 for once- versus twice-daily abacavir dosing\nwas 1.36 [90% confidence interval (CI) 1.11ââ?¬â??1.66]. The GM AUC0ââ?¬â??24 of once- and twice-daily lamivudine were 17.70 and\n18.11 mg.h/L, respectively. The GMR of AUC0ââ?¬â??24 for once- versus twice-daily lamivudine dosing was 0.98 (90% CI\n0.84ââ?¬â??1.14). At 96 weeks, 90% had HIV RNA <50 copies/mL and there were no serious adverse events.\nConclusion: Abacavir exposure was greater with once-daily dosing, while lamivudine once- and twice-daily exposures were\nbioequivalent. Once-daily abacavir and lamivudine using weight-band dosing is a treatment option for children.
Loading....