Dolutegravir versus Darunavir
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Study Design
In an open-label, multiple dose, 2-period, 2-sequence crossover study, healthy subjects received dolutegravir (DTG) 30 mg QD for 5 days (Period 1). In the second treatment period (Period 2), participants then received DTG 30 mg QD plus either lopinavir/ritonavir (LPV/r) 400/100mg Q 12h, or darunavir/ritonavir (DRV/r) 600/100mg Q 12h for 14 days, with no washout period in between. All doses were administered within 30 minutes of a moderately fatty meal. Blood samples for PK analysis were obtained on the last day of each treatment period.
Study Results
Co-administration of DTG + DRV/r resulted in a reduction of DTG pharmacokinetic (PK) parameters
PK study in HIV-infected patients also showed consistent result with the study done in healthy subjects. When HIV-infected patients were given DTG together with DRV/r, Cmin of DTG was significantly reduced compared to patients who were given DTG given alone
DRV/r led to DTG AUC, C max and C min decreases of 22, 11 and 38 %, respectively. Lopinavir/ritonavir did not significantly affect dolutegravir exposure, whereas darunavir/ritonavir decreased dolutegravir exposure by 11–38 %
Study Conclusions
This reduction was not deemed clinically significant, as the dolutegravir C trough was still ~7-fold higher than the in vitro, protein-adjusted IC90 despite use of a lower dose (30 mg) of dolutegravir than was assessed in phase II/III trials.
References
Cottrell ML, Hadzic T, Kashuba AD. Clinical pharmacokinetic, pharmacodynamic and drug-interaction profile of the integrase inhibitor dolutegravir. Clinical Pharmacokinetics. 2013; 11: 981-994.
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