Rilpivirine + Cabotegravir = 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 CAB 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 CAB and RPV, RPV (Ctau) decreased 8%, but had no effect on pharmacokinetic parameters of CAB.Geometric Least Squares Means Ratio (90% CI)Plasma PK ParameterGSK1265744 + RPV versus GSK1265744GSK1265744 + RPV versus RPVAUC1.12 (1.05, 1.19)0.987 (0.89, 1.09)Cmax1.05 (0.963, 1.15)0.963 (0.849, 1.09)Ctau1.14 (1.04, 1.24)0.919 (0.789, 1.07)

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.