Severe Renal Impairment Has Minimal Impact on Doravirine Pharmacokinetics [PublishAheadOfPrint]

Doravirine is a novel non-nucleoside reverse transcriptase inhibitor in development for use with other antiretroviral therapies to treat human immunodeficiency virus 1 (HIV-1) infection. Doravirine metabolism predominantly occurs via cytochrome P450 3A with <10% of elimination occurring via the renal pathway. As severe renal impairment can alter the pharmacokinetics (PK) of metabolically eliminated drugs, the effect of severe renal impairment on doravirine PK was assessed.

A single dose of doravirine 100 mg was administered to subjects aged 18–75 years with an estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73 m² (severe renal impairment group) and healthy controls with an eGFR of ≥80 mL/min/1.73 m², matched to the mean of the renal impairment group by age (±10 years) and weight (±10 kg). Doravirine plasma concentrations were determined at regular intervals and safety was monitored throughout.

The geometric mean ratios (90% confidence interval) for severe renal impairment/healthy subjects were 1.43 (1.00, 2.04), 1.38 (0.99, 1.92), and 0.83 (0.61, 1.15) for plasma doravirine area under the curve from zero to infinity (AUC_0–), plasma concentration at 24 hours post-dose (C₂₄), and maximum plasma concentration (C_max), respectively. Doravirine was generally well tolerated in both groups.

Based on the overall efficacy, safety, and PK profile of doravirine, the minor effect of severe renal impairment on doravirine PK observed in this study is not considered clinically meaningful.

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