BACKGROUND: Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor available as a single tablet and a three-drug combination with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) to treat HIV-1 infection. These analyses assessed pharmacokinetic (PK) interactions with co-administration.
METHODS: Two trials were conducted. Study 1: two-period, fixed-sequence; 8 healthy participants; Period 1, DOR 100 mg followed by ≥7-day washout; Period 2, TDF 300 mg once daily for 18 days, co-administration of DOR 100 mg on day 14. Study 2: three-period, crossover, 15 healthy participants; Treatment A, DOR 100 mg; Treatment B, 3TC 300 mg + TDF 300 mg; Treatment C, DOR 100 mg + 3TC 300 mg + TDF 300 mg; ≥7-day washout between periods.
RESULTS: Study 1: geometric mean ratios (GMRs) (90% confidence interval [CI]) of DOR AUC0–∞ and C24h (DOR + TDF / DOR) were 0.95 (0.80, 1.12) and 0.94 (0.78, 1.12), respectively. Study 2: GMRs (90% CI) of DOR AUC0–∞ and C24h (DOR + 3TC + TDF / DOR) were 0.96 (0.87, 1.06) and 0.94 (0.83, 1.06), respectively. GMRs (90% CI) of 3TC and tenofovir AUC0–∞ (DOR + 3TC + TDF / 3TC + TDF) were 0.94 (0.88, 1.00) and 1.11 (0.97, 1.28), respectively. Study drugs were generally well tolerated.
CONCLUSIONS: Multiple doses of TDF did not have a clinically meaningful effect on DOR PK. The PK of DOR were similar when administered alone or in combination with 3TC and TDF. DOR had no meaningful effect on the PK of 3TC and tenofovir.
Recommended CitationAnderson, Matt S.; Gilmartin, Jocelyn; Fan, Li; Yee, Ka Lai; Kraft, Walter K.; Triantafyllou, Ilias; Reitmann, Christina; Guo, Ying; Liu, Rachael; and Iwamoto, Marian, "No meaningful drug interactions with doravirine, lamivudine and tenofovir disoproxil fumarate co-administration." (2019). Department of Pharmacology and Experimental Therapeutics Faculty Papers. Paper 110.