No clinically significant pharmacokinetic interactions between dolutegravir and daclatasvir in healthy adult subjects.
BACKGROUND
Daclatasvir (DCV) is an NS5A replication complex inhibitor recently approved for chronic hepatitis C virus treatment.


METHODS
To assess drug interactions between the HIV integrase strand transfer inhibitor dolutegravir (DTG) and DCV, subjects were randomized into 1 of 2 sequences in an open-label, 3-period, crossover study. Subjects received either DTG 50 mg once daily or DCV 60 mg once daily for 5 days in periods 1 and 2 and DTG 50 mg plus DCV 60 mg once daily for 5 days in period 3, with no washout between periods 2 and 3. Between periods 1 and 2, there was a washout period of at least 7 days.


RESULTS
The geometric least-squares mean ratios (90 % confidence intervals) of DCV area under the concentration-time curve over a dosing interval (AUC0-τ), maximum observed concentration (Cmax), and concentration at the end of the dosing interval (Cτ) were 0.978 (0.831-1.15), 1.03 (0.843-1.25), and 1.06 (0.876-1.29), respectively, when DCV was administered with DTG compared with DCV alone. Compared with DTG alone, coadministration of DTG with DCV increased DTG AUC0-τ, Cmax, and Cτ by approximately 33, 29, and 45 %, respectively.


CONCLUSIONS
DCV plasma exposure was not meaningfully affected by DTG. Coadministration of DTG with DCV resulted in slight increases in DTG AUC0-τ, Cmax, and Cτ. Accumulated safety and tolerability data in humans receiving DTG to date suggests this effect is not considered clinically significant. DTG and DCV can be coadministered without dose adjustment.


TRIAL REGISTRATION
Registered on March 6, 2014 with ClinicalTrials.gov; registration number: NCT02082808 and as Study ID: 201102 on the ViiV Clinical Study Registry.
['Ross|Lisa L|LL|', 'Song|Ivy H|IH|', 'Arya|Niki|N|', 'Choukour|Mike|M|', 'Zong|Jian|J|', 'Huang|Shu-Pang|SP|', 'Eley|Timothy|T|', 'Wynne|Brian|B|', 'Buchanan|Ann M|AM|']
D000293:Adolescent D000328:Adult D000368:Aged D000998:Antiviral Agents D019540:Area Under Curve D002219:Carbamates D018592:Cross-Over Studies D004334:Drug Administration Schedule D004347:Drug Interactions D005260:Female D019428:HIV Integrase Inhibitors D064368:Healthy Volunteers D006575:Heterocyclic Compounds, 3-Ring D006801:Humans D007093:Imidazoles D008297:Male D008875:Middle Aged D017063:Outcome Assessment, Health Care D010078:Oxazines D010879:Piperazines D011728:Pyridones D011759:Pyrrolidines D014633:Valine D055815:Young Adult
Pharmacokinetics Interactions Drug interactions Adult medicine Infectious disease