Antivir Ther. 2010;15(3):297-305. doi: 10.3851/IMP1532.
Once-daily dosing of abacavir and lamivudine has been approved for adults, but paediatric data are insufficient. We conducted a pharmacokinetic study of once-daily and twice-daily abacavir and lamivudine in children aged 3-<36 months.
Children with stable HIV type-1 (HIV-1) RNA levels after 12 weeks treatment with twice-daily abacavir (8 mg/kg) with or without lamivudine (4 mg/kg) underwent plasma pharmacokinetic sampling. Children then switched to once-daily abacavir (16 mg/kg) with or without lamivudine (8 mg/kg), and sampling was repeated 4 weeks later. The area under the plasma concentration-time curve over 24 h (AUC(0-24)) and the maximum concentration (C(max)) were compared using geometric mean ratios (GMRs); 90% confidence intervals (CIs) within the range of 0.80-1.25 were considered bioequivalent.
A total of 18 children (4, 6 and 8 in the 3-<12, 12-<24 and 24-<36 month age ranges, respectively) provided pharmacokinetic data for abacavir (17 for lamivudine). The GMR of AUC(0-24), once-daily versus twice-daily, was 1.07 (90% CI 0.92-1.23) for abacavir and 0.91 (90% CI 0.79-1.06) for lamivudine. C(max) almost doubled on once-daily versus twice-daily dosing: abacavir and lamivudine GMRs were 2.04 (90% CI 1.73-2.42) and 1.78 (90% CI 1.52-2.09), respectively. At baseline, 12, 24 and 48 weeks, 89%, 94%, 100% and 89% of children had HIV-1 RNA<400 copies/ml, respectively.
Bioequivalence was demonstrated on AUC(0-24) between twice-daily and once-daily abacavir; very similar AUC(0-24) values were seen for twice-daily and once-daily lamivudine. Given that viral load suppression rates were maintained, these data suggest that once-daily abacavir and lamivudine might be an option for children aged 3-<36 months.
阿巴卡韦和拉米夫定每日一次给药已获批准用于成人，但儿科数据不足。我们对3至36个月以下儿童进行了阿巴卡韦和拉米夫定每日一次及每日两次给药的药代动力学研究。
在接受每日两次阿巴卡韦（8毫克/千克）联合或不联合拉米夫定（4毫克/千克）治疗12周后，HIV-1 RNA水平稳定的儿童进行血浆药代动力学采样。然后这些儿童改用每日一次阿巴卡韦（16毫克/千克）联合或不联合拉米夫定（8毫克/千克），4周后重复采样。使用几何平均比值（GMRs）比较24小时血浆浓度-时间曲线下面积（AUC(0-24)）和最大浓度（C(max)）；90%置信区间（CIs）在0.80至1.25范围内被认为具有生物等效性。
共有18名儿童（3至12个月、12至24个月和24至36个月年龄组分别有4名、6名和8名）提供了阿巴卡韦的药代动力学数据（17名提供了拉米夫定的药代动力学数据）。阿巴卡韦每日一次与每日两次给药的AUC(0-24)的GMR为1.07（90% CI 0.92至1.23），拉米夫定的为0.91（90% CI 0.79至1.06）。每日一次给药的C(max)几乎是每日两次给药的两倍：阿巴卡韦和拉米夫定的GMR分别为2.04（90% CI 1.73至2.42）和1.78（90% CI 1.52至2.09）。在基线、12周、24周和48周时，分别有89%、94%、100%和89%的儿童HIV-1 RNA<400拷贝/毫升。
每日两次和每日一次阿巴卡韦在AUC(0-24)上显示出生物等效性；每日两次和每日一次拉米夫定的AUC(0-24)值非常相似。鉴于病毒载量抑制率得以维持，这些数据表明每日一次阿巴卡韦和拉米夫定可能是3至36个月以下儿童的一种选择。
