Dolutegravir + Rilpivirine = Unknown or no reaction

Study Design

Ford, et al, conducted a phase 1, open-label, two-cohort, three-period, single-sequence crossover study to evaluate the effect of oral coadministration of rilpivirine (RPV) with dolutegravir (DTG, n = 16) on the pharmacokinetic parameters of these agents.Healthy (HIV negative) subjects received DTG (50 mg every 24 h for 5 days) in period 1 followed by a washout of at least seven days, RPV (25 mg every 24 h for 11 or 12 days) in period 2, immediately followed by RPV (25 mg every 24 h) plus DTG (50 mg every 24 h) for 5 days in period 3. No washout was needed between periods two and three as steady state data for both rilpivirine and the integrase inhibitor had already been collected. Steady-state pharmacokinetic (PK) parameters were estimated using noncompartmental analysis of data collected on the last day of each period.

Study Results

The combination of RPV and DTG was well tolerated; no grade 3 or 4 adverse events (AEs) or AE-related discontinuations were observed. The 90% confidence intervals for the area under the curve from time zero until the end of the dosage interval [AUC] and maximum concentration of drug in serum (Cmax) geometric mean ratios were within 0.8 to 1.25. Following administration of DTG and RPV, DTG and RPV (Ctau) increased by 22% and 21%, respectively.Geometric Least Squares Means Ratio (90% CI)Plasma PK ParameterDTG + RPV versus DTGDTG + RPV versus RPVAUC1.12 (1.05, 1.19)1.06 (0.976, 1.16)Cmax1.13 (1.06, 1.21)1.1 (0.992, 1.22)Ctau1.22 (1.15, 1.3)1.21 (1.07, 1.38)

Study Conclusions

References

Susan L Ford, Elizabeth Gould, Shuguang Chen, David Margolis, William Spreen, Herta Crauwels, Stephen Piscitelli. Lack of pharmacokinetic interaction between rilpivirine and integrase inhibitors dolutegravir and gsk1265744. Antimicrobial Agents And Chemotherapy. 2013; 11: 5472-5477.