Twice-Daily Doravirine Overcomes the Interaction Effect from Once-Weekly Rifapentine and Isoniazid in Healthy Volunteers.

Authors

Edwin Lam, Thomas Jefferson UniversityFollow
Joseph Schaefer, Thomas Jefferson UniversityFollow
Richard Zheng, Thomas Jefferson UniversityFollow
Tingting Zhan, Thomas Jefferson UniversityFollow
Walter K. Kraft, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

5-14-2020

Comments

This article is the authors' final version prior to publication in Clinical and Translational Science, May 2020, Pages 758-762.

The published version is available at https://doi.org/10.1111/cts.12810. Copyright © Lam et al.

Abstract

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 AUC_0‐12 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 Citation

Lam, 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.
https://jdc.jefferson.edu/petfp/120

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

PubMed ID

32407548

Language

English