The limitations of this study include that it was a small study of only 12 subjects, the interaction was not evaluated in HIV-infected individuals, therefore, pharmacokinetics may be changed when studied in HIV-infected subjects, and the study was not with repeated dosing of dolutegravir.
Dolutegravir vs antacids, vitamins, and minerals
^
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
The authors found that co-administration of omeprazole only minimally decreased plasma exposure of dolutegravir. The authors determined the GLS mean ratios for the above stated PK parameters ranged from 0.92-1.00 and 90% confidence intervals within the bounds 0.75-1.25. The authors state that from their findings they feel that dolutegravir can be co-administered with PPIs and H-2 receptor antagonists without dose adjustment.
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.
icon on your home screen.