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A Study to Evaluate Doravirine Pharmacokinetics When Coadministered With Acid-Reducing Agents.
- Source :
-
Journal of clinical pharmacology [J Clin Pharmacol] 2019 Aug; Vol. 59 (8), pp. 1093-1098. Date of Electronic Publication: 2019 Feb 28. - Publication Year :
- 2019
-
Abstract
- Doravirine is a novel non-nucleoside reverse transcriptase inhibitor indicated for the treatment of human immunodeficiency virus type 1 infection. Because of potential concomitant administration with acid-reducing agents, a drug-interaction trial was conducted to evaluate the potential impact of these types of medications on doravirine pharmacokinetics. In an open-label, 3-period, fixed-sequence trial, healthy adult participants received the following: period 1, a single dose of doravirine 100 mg; period 2, coadministration of a single dose of doravirine 100 mg and an antacid (1600 mg aluminum hydroxide, 1600 mg magnesium hydroxide, and 160 mg simethicone); period 3, 40 mg pantoprazole once daily on days 1-5 coadministered with a single dose of doravirine 100 mg on day 5. There was a minimum 10-day washout between periods. Plasma samples for pharmacokinetic evaluation were collected, and safety was assessed. Fourteen participants (8 male, 6 female) were enrolled, and 13 completed the trial. Geometric mean ratios (90% confidence intervals) for doravirine AUC <subscript>0-inf</subscript> , C <subscript>max</subscript> , and C <subscript>24</subscript> for doravirine + antacid/doravirine were 1.01 (0.92-1.11), 0.86 (0.74-1.01), and 1.03 (0.94-1.12), respectively, and for doravirine + pantoprazole/doravirine were 0.83 (0.76-0.91), 0.88 (0.76-1.01), and 0.84 (0.77-0.92), respectively. Doravirine was generally well tolerated administered alone or with either of the acid-reducing agents. Coadministration of an aluminum/magnesium-containing antacid or pantoprazole did not have a clinically meaningful effect on doravirine pharmacokinetics, supporting the use of acid-reducing agents with doravirine.<br /> (© 2019, The American College of Clinical Pharmacology.)
- Subjects :
- Adult
Drug Interactions
Female
Humans
Male
Middle Aged
Aluminum Hydroxide pharmacology
Antacids pharmacology
Magnesium Hydroxide pharmacology
Pantoprazole pharmacology
Proton Pump Inhibitors pharmacology
Pyridones pharmacokinetics
Reverse Transcriptase Inhibitors pharmacokinetics
Simethicone pharmacology
Triazoles pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4604
- Volume :
- 59
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of clinical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 30817001
- Full Text :
- https://doi.org/10.1002/jcph.1399