Han Kelong, Abulfathi Ahmed A, Mehta Rashmi S, Nand Romina A, Marzinke Mark A, Landovitz Raphael J, D'Amico Ronald D, Rinehart Alex R, Spreen William R, Ford Susan L
Int J Clin Pharmacol Ther. 2025 Sep;63(9):427-431. doi: 10.5414/CP204849.
Cabotegravir is approved for HIV treatment (with rilpivirine) and prevention. The established cabotegravir population pharmacokinetic (PPK) model included 1.2% Asian participants. We aimed to compare cabotegravir pharmacokinetics between Asian and non-Asian populations and across Asian countries.
Cabotegravir concentrations were collected from Asian participants in phase 1 and 3 studies. The applicability of the PPK model to Asian populations was validated by predicting the observed concentrations not included in model-building. Cabotegravir post-hoc pharmacokinetic parameters (long-acting absorption rate constant, weight-normalized apparent clearances and volumes of distribution) and exposures (trough and peak concentrations) following monthly and every-2-month regimens were estimated by fitting the PPK model to observed data. Non-Asian participants from the previous PPK dataset (1,697 males; 564 females) were used as comparator. Cabotegravir exposures in Asian and non-Asian were compared via simulations.
2,034 cabotegravir concentrations were collected from 162 Asian males (assigned male at birth) in China (n = 47), Japan (n = 17), Korea (n = 25), Thailand (n = 53), and Vietnam (n = 20), and 35 concentrations from 2 Asian females (assigned female at birth) in Korea. Cabotegravir pharmacokinetic parameters were similar between Asian and non-Asian participants. Cabotegravir exposures in Asian populations largely overlapped with but tended to be higher than non-Asian populations, suggesting similar efficacy. Cabotegravir exposures in Asian and non-Asian populations remained below the safety threshold, suggesting similar safety profiles. Cabotegravir pharmacokinetic parameters and exposures were similar across Asian countries.
No dose adjustment is recommended for Asian populations with and without HIV. Cabotegravir pharmacokinetic data from any Asian country/region may guide pharmacokinetic evaluation and regulatory considerations across Asian regions.
卡博特韦已被批准用于HIV治疗（与利匹韦林联用）及预防。已建立的卡博特韦群体药代动力学（PPK）模型纳入的亚洲参与者仅占1.2%。我们旨在比较亚洲和非亚洲人群以及亚洲各国之间卡博特韦的药代动力学情况。
收集了1期和3期研究中亚洲参与者的卡博特韦浓度数据。通过预测模型构建中未包含的观测浓度，验证了PPK模型对亚洲人群的适用性。通过将PPK模型与观测数据拟合，估算了每月和每两个月给药方案后的卡博特韦事后药代动力学参数（长效吸收速率常数、体重标准化表观清除率和分布容积）以及暴露量（谷浓度和峰浓度）。将先前PPK数据集中的非亚洲参与者（1697名男性；564名女性）用作对照。通过模拟比较了亚洲和非亚洲人群中卡博特韦的暴露量。
从中国（n = 47）、日本（n = 17）、韩国（n = 25）、泰国（n = 53）和越南（n = 20）的162名亚洲男性（出生时被指定为男性）中收集了2034份卡博特韦浓度数据，从韩国的2名亚洲女性（出生时被指定为女性）中收集了35份浓度数据。亚洲和非亚洲参与者的卡博特韦药代动力学参数相似。亚洲人群中卡博特韦的暴露量与非亚洲人群基本重叠，但往往更高，提示疗效相似。亚洲和非亚洲人群中卡博特韦的暴露量均低于安全阈值，提示安全性相似。亚洲各国之间卡博特韦的药代动力学参数和暴露量相似。
对于有或无HIV的亚洲人群，不建议调整剂量。来自任何亚洲国家/地区的卡博特韦药代动力学数据均可指导亚洲各地区的药代动力学评估及监管考量。
