Objectives. Evaluation of pharmacokinetics and pharmacodynamics of darunavir and etravirine among HIV-1ââ?¬â??infected, treatmentexperienced\r\nadults from GRACE, by sex and race.Methods. Patients received darunavir/ritonavir 600/100mg twice daily plus other\r\nantiretrovirals, which could include etravirine 200mg twice daily. Population pharmacokinetics for darunavir and etravirine were\r\ndetermined over 48 weeks and relationships assessed with virologic response and safety. Rich sampling for darunavir, etravirine,\r\nand ritonavir was collected in a substudy at weeks 4, 24, and 48. Results. Pharmacokinetics were estimated in 376 patients for\r\ndarunavir and 190 patients for etravirine. Median darunavir AUC12h and C0h were 60,642ngÃ?·h/mL and 3624ng/mL, respectively;\r\nand for etravirine were 4183ng Ã?· h/mL and 280ng/mL, respectively. There were no differences in darunavir or etravirine AUC12h or\r\nC0h by sex or race. Age, body weight, or use of etravirine did not affect darunavir exposure. No relationships were seen between\r\ndarunavir pharmacokinetics and efficacy or safety. Patients with etravirine exposure in the lowest quartile generally had lower\r\nresponse rates. Rich sampling showed no time-dependent relationship for darunavir, etravirine, or ritonavir exposure over 48\r\nweeks. Conclusions. Population pharmacokinetics showed no relevant differences in darunavir or etravirine exposure by assessed\r\ncovariates. Lower etravirine exposures were associated with lower response rates.
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