Dolutegravir + Simethicone = Precautionary

Study Design

This was an open-label, randomized, cross-over study of 12 healthy men and women in a two treatment period study. Subjects were given 50mg of dolutegravir in treatment period 1. Then, with no washout period subjects entered into treatment period 2 where they received 40mg of omeprazole daily for 5 days. On day 5, 2 hours after the omeprazole dose, subjects received a 50mg dose of dolutegravir. Serial pharmacokinetic (PK) samples were obtained in each treatment period to determine the plasma concentration of dolutegravir. PK parameters that were determined were AUC(0-infinity), AUC(0-t) (t=time of the last quantifiable concentration), Cmax, and C24 (the plasma concentration 24 hours after the study drug dose). The ratios of geometric least squares (GLS) means and associated 90% confidence intervals were estimated for these parameters.

Study Results

16 subjects completed the study and all of the subjects were male. Simultaneous administration of dolutegravir with an antacid significantly reduced the dolutegravir plasma exposure. This interaction was significantly improved by administering dolutegravir 2 hours before the antacid. GLS mean ratios and 90% CIs were 0.26 (0.22, 0.32) for AUC0-∞, 0.28 (0.23, 0.33) for Cmax, 0.26 (0.21, 0.31) for C24, and 0.74 (0.61, 0.89) for AUC0-t, 0.82 (0.69, 0.98) for Cmax and 0.70 (0.58, 0.85) for C24, respectively. The author's recommendation is that dolutegravir can be administered 2 hours before or 6 hours after an antacid without dose adjustment.

Study Conclusions

References

Parul Patel, Ivy Song, Julie Borland, Apurva Patel, Yu Lou, Shuguang Chen, Toshihiro Wajima, Amanda Peppercorn, Sherene S Min, Stephen C Piscitelli. Pharmacokinetics of the hiv integrase inhibitor s/gsk1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Journal Of Antimicrobial Chemotherapy. 2011; : 139.