Pharmacokinetics and Pharmacodynamics of Darunavir and Etravirine in HIV-1–Infected, Treatment-Experienced Patients in the Gender, Race, and Clinical Experience (GRACE) Trial
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...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | AIDS Research and Treatment |
| Online Access: | http://dx.doi.org/10.1155/2012/186987 |
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| _version_ | 1850158258998738944 |
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| author | Thomas Kakuda Vanitha Sekar Peter Vis Bruce Coate Robert Ryan David Anderson Guy De La Rosa Joseph Mrus |
| author_facet | Thomas Kakuda Vanitha Sekar Peter Vis Bruce Coate Robert Ryan David Anderson Guy De La Rosa Joseph Mrus |
| author_sort | Thomas Kakuda |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-69d57b1edb1e4c86a84e063601f34ea0 |
| institution | OA Journals |
| issn | 2090-1240 2090-1259 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | AIDS Research and Treatment |
| spelling | doaj-art-69d57b1edb1e4c86a84e063601f34ea02025-08-20T02:23:56ZengWileyAIDS Research and Treatment2090-12402090-12592012-01-01201210.1155/2012/186987186987Pharmacokinetics and Pharmacodynamics of Darunavir and Etravirine in HIV-1–Infected, Treatment-Experienced Patients in the Gender, Race, and Clinical Experience (GRACE) TrialThomas Kakuda0Vanitha Sekar1Peter Vis2Bruce Coate3Robert Ryan4David Anderson5Guy De La Rosa6Joseph Mrus7Janssen Research & Development, LLC., Clinical Pharmacology, 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USAJanssen Research & Development, LLC., Clinical Pharmacology, 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USAJanssen Infectious Diseases BVBA, Clinical Pharmacology, Turnhoutseweg 30, B-2340 Beerse, BelgiumJanssen Research & Development, LLC., Medical Affairs Biometrics, 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USAJanssen Research & Development, LLC., Medical Affairs Biometrics, 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USAJanssen Services, LLC., Clinical Affairs, 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USAJanssen Services, LLC., Clinical Affairs, 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USAJanssen Services, LLC., Clinical Affairs, 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USAObjectives. 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.http://dx.doi.org/10.1155/2012/186987 |
| spellingShingle | Thomas Kakuda Vanitha Sekar Peter Vis Bruce Coate Robert Ryan David Anderson Guy De La Rosa Joseph Mrus Pharmacokinetics and Pharmacodynamics of Darunavir and Etravirine in HIV-1–Infected, Treatment-Experienced Patients in the Gender, Race, and Clinical Experience (GRACE) Trial AIDS Research and Treatment |
| title | Pharmacokinetics and Pharmacodynamics of Darunavir and Etravirine in HIV-1–Infected, Treatment-Experienced Patients in the Gender, Race, and Clinical Experience (GRACE) Trial |
| title_full | Pharmacokinetics and Pharmacodynamics of Darunavir and Etravirine in HIV-1–Infected, Treatment-Experienced Patients in the Gender, Race, and Clinical Experience (GRACE) Trial |
| title_fullStr | Pharmacokinetics and Pharmacodynamics of Darunavir and Etravirine in HIV-1–Infected, Treatment-Experienced Patients in the Gender, Race, and Clinical Experience (GRACE) Trial |
| title_full_unstemmed | Pharmacokinetics and Pharmacodynamics of Darunavir and Etravirine in HIV-1–Infected, Treatment-Experienced Patients in the Gender, Race, and Clinical Experience (GRACE) Trial |
| title_short | Pharmacokinetics and Pharmacodynamics of Darunavir and Etravirine in HIV-1–Infected, Treatment-Experienced Patients in the Gender, Race, and Clinical Experience (GRACE) Trial |
| title_sort | pharmacokinetics and pharmacodynamics of darunavir and etravirine in hiv 1 infected treatment experienced patients in the gender race and clinical experience grace trial |
| url | http://dx.doi.org/10.1155/2012/186987 |
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