International journal of clinical pharmacology and therapeutics · 2025
Cabotegravir pharmacokinetics in Asians with and without HIV.
СтатьяСравнительное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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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
Аннотация
OBJECTIVE: 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.
MATERIALS AND METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
MATERIALS AND METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.