Pharmacokinetic Interaction Between Anti-TB Agent Rifabutin and HIV Drug Rilpivirine: Presented at AIDS 2008

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Title: Pharmacokinetic Interaction Between Anti-TB Agent Rifabutin and HIV Drug Rilpivirine: Presented at AIDS 2008
URL: http://www.pslgroup.com/dg/2278CE.htm
Doctor's Guide
August 8, 2008

By Kate Jongbloed

MEXICO CITY -- August 8, 2008 -- Clinical tests indicate an interaction between the antituberculosis drug rifabutin and the investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine that appears to affect the pharmacokinetics of rilpivirine, researchers explained here at the 17th International AIDS Conference (AIDS 2008).

A dosing schedule to overcome the drug-drug interaction between the two agents, therefore, needs to be worked out, noted lead investigator Herta Crauwels, PharmD, Tibotec, Inc., Mechelen, Belgium.

Since tuberculosis-HIV coinfection tends to occur frequently, doctors will possibly choose to treat patients with both rifabutin and rilpivirine -- hence the need to determine the pharmacokinetics of their interaction.

In a poster presentation delivered here on August 5, Dr. Crauwels reported that the interaction between rifabutin and rilpivirine reduces plasma concentrations of rilpivirine.

Dr. Crauwels highlighted the role of cytochrome P450 3A4 (CYP3A4) in the metabolism of the substrate, initiated by rifabutin. Rifabutin, a known CYP3A4 inducer, initiates the enzyme's metabolism of rilpivirine, leading to the reduction of rilpivirine's plasma concentrations.

Dr. Crauwels and colleagues recruited 18 antiretroviral-naïve, HIV-negative volunteers for this open-label, randomised, crossover trial. All subjects were Caucasian nonsmokers between the ages of 22 and 52 years.

Participants were divided into 3 groups: The first group received rilpivirine 150 mg/day, while the second group received rifabutin 300 mg/day; the third group received both rilpivirine and rifabutin in the same doses. In all groups, the drugs were taken after breakfast for 11 days.

Calculating minimum plasma concentration and the area under the plasma concentration-time curve over 24 hours from dosing, the research team was able to identify a 49% reduction in rilpivirine plasma concentration in patients receiving rilpivirine alone and a 46% reduction in rilpivirine plasma concentration in patients taking the rilpivirine and rifabutin combination.

Dr. Crauwels noted, however, that "rilpivirine did not affect the exposure to rifabutin or its active metabolite."

Ninety-four percent of participants reported 1 or more adverse events, including headache, chromaturia, increase in lipase, and increase in triglycerides, although Dr. Crauwels noted, "All treatments were generally safe and well tolerated."

Rilpivirine is designed to overcome resistant viruses that limit the use of current NNRTIs efavirenz and nevirapine.

[Presentation title: The Pharmacokinetic (PK) Interaction Between Rifabutin and TMC278, an Investigational Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI). Abstract TUPE0080]

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