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AIDS Res Treat. 2012; 2012: 186987.
Published online Mar 21, 2012. doi:  10.1155/2012/186987
PMCID: PMC3318205
Pharmacokinetics and Pharmacodynamics of Darunavir and Etravirine in HIV-1–Infected, Treatment-Experienced Patients in the Gender, Race, and Clinical Experience (GRACE) Trial
Thomas Kakuda, 1 * Vanitha Sekar, 1 Peter Vis, 2 Bruce Coate, 3 Robert Ryan, 3 David Anderson, 4 Guy De La Rosa, 4 and Joseph Mrus 4
1Janssen Research & Development, LLC., Clinical Pharmacology, 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USA
2Janssen Infectious Diseases BVBA, Clinical Pharmacology, Turnhoutseweg 30, B-2340 Beerse, Belgium
3Janssen Research & Development, LLC., Medical Affairs Biometrics, 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USA
4Janssen Services, LLC., Clinical Affairs, 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USA
*Thomas Kakuda: tkakuda/at/its.jnj.com
Academic Editor: Qing Ma
Received October 12, 2011; Accepted November 29, 2011.
Abstract
Objectives. Evaluation of pharmacokinetics and pharmacodynamics of darunavir and etravirine among HIV-1–infected, treatment-experienced adults from GRACE, by sex and race. Methods. Patients received darunavir/ritonavir 600/100mg twice daily plus other antiretrovirals, which could include etravirine 200mg twice daily. Population pharmacokinetics for darunavir and etravirine were determined over 48 weeks and relationships assessed with virologic response and safety. Rich sampling for darunavir, etravirine, and ritonavir was collected in a substudy at weeks 4, 24, and 48. Results. Pharmacokinetics were estimated in 376 patients for darunavir and 190 patients for etravirine. Median darunavir AUC12h and C0h were 60,642ng·h/mL and 3624ng/mL, respectively; and for etravirine were 4183ng · h/mL and 280ng/mL, respectively. There were no differences in darunavir or etravirine AUC12h or C0h by sex or race. Age, body weight, or use of etravirine did not affect darunavir exposure. No relationships were seen between darunavir pharmacokinetics and efficacy or safety. Patients with etravirine exposure in the lowest quartile generally had lower response rates. Rich sampling showed no time-dependent relationship for darunavir, etravirine, or ritonavir exposure over 48 weeks. Conclusions. Population pharmacokinetics showed no relevant differences in darunavir or etravirine exposure by assessed covariates. Lower etravirine exposures were associated with lower response rates.
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