Pharmacokinetics and safety of dolutegravir in healthy Japanese subjects

: Dolutegravir (DTG) is a once-daily, unboosted integrase inhibitor that has been shown to be effective by once daily dosing. The impact of race on dolutegravir pharmacokinetics has not yet been fully characterized. This study was a Phase 1, open label, single dose study to determine pharmacokinetics (PK), safety and tolerability of DTG following 50mg single oral administration in the fasted state in healthy adult Japanese subjects. Subjects had a screening visit within 30 days prior to the administration of study drug, and a follow-up visit within 7 to 14 days after the administration of study drug. Safety evaluation and serial PK samplings were performed pre-dose and for 72 hours after dosing. Non-compartmental analysis was performed for PK parameter calculation. Data were compared to historical values from a similar Phase 1 study conducted in non-Asian, healthy adult subjects (n = 18, 17 Caucasian and 1 Arabic/North African). Ten subjects were enrolled and completed the study. DTG was well tolerated with no adverse events reported throughout the study period. Geometric means (CV%) of single dose DTG PK parameters in Japanese subjects for C(max), AUC(inf), t1/2 and C24 were 2.14microg/mL (47%), 43.4 microg x hr/mL (46%), 14.6 hours (10%) and 0.67 microg/mL (45%). The pharmacokinetics and safety profiles of DTG following single dose oral administration to Japanese healthy adult subjects were consistent with findings previously observed in non-Japanese healthy adult subjects. DTG may be given to Japanese subjects without dose-adjustment.