Clinical Pharmacokinetics and Drug Interactions of Doravirine

Abstract

Doravirine is a new HIV-1 non-nucleoside reverse transcriptase inhibitor that has demonstrated a good efficacy and safety profile in clinical trials. It has a therapeutic profile that makes it an attractive option for treatment of HIV-1 infection. As such, there has been an increase in the published literature regarding the pharmacokinetics of doravirine and potential for drug-drug interactions. This review aimed to identify pharmacokinetic literature pertaining to doravirine, used findings from the literature to summarize its pharmacokinetic profile, and finally evaluated literature describing actual and potential drug interactions. Review findings show doravirine is well-absorbed, exhibits moderate protein binding activity, and is extensively metabolized by cytochrome P450 enzymes (specifically CYP3A). It has an elimination half-life of 12-21 h. Gender, age, moderate hepatic impairment, and co-administration with food did not greatly alter doravirine's pharmacokinetic profile. Drug interaction studies have shown doravirine does not affect the pharmacokinetics of dolutegravir or atorvastatin but may have its pharmacokinetics altered by rifampicin (rifampin) and other rifamycins (CYP3A inducers) and ritonavir (CYP3A inhibitor). No clinically significant interactions were noted between doravirine and an antacid (aluminum-magnesium), pantoprazole, ledipasvir/sofosbuvir, or elbasvir/grazoprevir. Further study is needed to better understand doravirine's efficacy and safety profile when co-administered with other agents known to be CYP inducers or inhibitors.