Moderate Hepatic Impairment Does Not Affect Doravirine Pharmacokinetics

Area of Science:

• Pharmacology
• Hepatology
• Infectious Diseases

Background:

• Doravirine is a potent nonnucleoside reverse-transcriptase inhibitor for HIV-1 treatment.
• CYP3A metabolism suggests potential for drug interactions with liver function changes.
• A significant portion of the HIV-1 population experiences varying degrees of liver impairment.

Purpose of the Study:

• To assess the impact of moderate hepatic impairment on doravirine pharmacokinetics.
• To evaluate the tolerability of single-dose doravirine in subjects with liver impairment.
• To determine if dose adjustments are necessary for HIV-1 patients with moderate liver dysfunction.

Main Methods:

• Open-label, single-dose trial of 100 mg doravirine.
• 16 subjects: 8 with moderate hepatic impairment (Child-Pugh 7-9) and 8 healthy controls.
• Pharmacokinetic profiling including AUC, Cmax, and terminal half-life.

Main Results:

• Doravirine exposure (AUC0-∞, AUC0-24h, Cmax, C24h) was similar between groups.
• Geometric mean terminal half-life was approximately 18 hours in both impaired and healthy subjects.
• Doravirine was generally well-tolerated with no significant adverse events reported.

Conclusions:

• Moderate hepatic impairment does not produce clinically significant changes in doravirine pharmacokinetics.
• Dose adjustment of doravirine is not required for patients with HIV-1 and moderate hepatic impairment.
• Doravirine demonstrates a favorable safety and pharmacokinetic profile in this population.