Dolutegravir + Copper = 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 a multivitamin had a relatively limited effect on the PK of a single dose of dolutegravir, with GLS mean ratios for PK parameters ranging from 0.64 to 0.67 and 90% CIs within the bounds 0.54-0.82. The authors stated that although there was a slight decrease in the mean C24 plasma concentration of dolutegravir 50mg as a single dose, co-administered with a multivitamin is still 5.3-fold greater than the in-vitro PA-IC90. (See footnote section for recomendation)

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.