Doravirine (DOR) is a non‐nucleoside reverse transcriptase inhibitor indicated for the treatment of human immunodeficiency virus‐1 (HIV‐1). Its use in combination with rifapentine (RPT), an anti‐tuberculosis antibiotic, may reduce the exposure of DOR compromising viral suppression in those living with HIV‐1 co‐infected with tuberculosis. We conducted a prospective, phase I, open label, two‐period, fixed sequence, drug interaction study to evaluate the effect of once‐weekly RPT and isoniazid (INH) on the pharmacokinetics of DOR in healthy volunteers. DOR 100 mg was administered alone twice‐daily for 4 days in period 1. In period 2, once‐weekly RPT+INH was co‐administered with multiple doses of DOR 100 mg twice‐daily for study days 7, 14, and 21. Plasma was obtained for DOR pharmacokinetics when given alone and co‐administered with RPT+INH. Eleven healthy volunteers enrolled and completed the study. The geometric mean ratios and 90% confidence intervals for DOR AUC0‐12 and C12 in the presence of RPT+INH compared to DOR alone were 0.71 (0.60‐0.85) and 0.69 (0.54‐0.89), respectively. Although exposures were moderately reduced in the presence of RPT+INH, trough DOR values were within the concentration range associated with virological suppression. These results demonstrate that a modest decrease in doravirine exposure would unlikely be clinically relevant in a virally suppressed patient co‐administered once‐weekly RPT+INH.
Recommended CitationLam, Edwin; Schaefer, Joseph; Zheng, Richard; Zhan, Tingting; and Kraft, Walter K., "Twice-Daily Doravirine Overcomes the Interaction Effect from Once-Weekly Rifapentine and Isoniazid in Healthy Volunteers." (2020). Department of Pharmacology and Experimental Therapeutics Faculty Papers. Paper 120.
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