Print this page    •   Back to Web version of article

The Body Covers: The 12th International AIDS Conference

Pharmacokinetics of MKC-422, One of the Next Non-nucleoside Reverse Transcriptase Inhibitors, Together with ZDV, 3TC, d4T, and ddI

Coverage provided by Ian Frank, M.D.

June 29, 1998

MKC-442 is a non-nucleoside reverse transcriptase inhibitor with potent activity in early phase I/II studies. Prior to moving forward with larger trials testing the drug's activity, this pharmacokinetic study was conducted to investigate the possible interactions between the drug and ZDV, 3TC, d4T, and ddI. MKC-422 is metabolized by the cytochrome P450 liver enzyme CYP3A4, the enzyme responsible for metabolizing the other non-nucleoside reverse transcriptase inhibitors as well as the protease inhibitors. Other NNRTIs and protease inhibitors have not been shown to have any effects on the pharmacokinetics of the nucleoside reverse transcriptase inhibitors, and none was expected in this study.

30 uninfected men and women volunteered for the study and took either MKC-442 alone, the combination of ZDV + 3TC or d4T + ddI, or MKC-442 together with ZDV + 3TC or d4T + ddI. Concentrations of MKC-442 were not effected by either of the nucleoside combinations. However, peak concentrations of ZDV and the area under the curve (a calculation of the total drug exposure following a single dose) were elevated by 50% when taken together with MKC-422, suggesting that MKC-422 inhibits the metabolism and/or secretion of ZDV. This was an unexpected finding. The mechanism for this interaction is under investigation, and its clinical significance is being studied in clinical studies of the combination.

This article was provided by Copyright Body Health Resources Corporation. All rights reserved.

You can find this article online by typing the following address into your Web browser:

Please Note: Knowledge about HIV changes rapidly. Note the date of this article's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this article.

General Disclaimer: The Body is designed for educational purposes only and is not engaged in rendering medical advice or professional services. The information provided through The Body should not be used for diagnosing or treating a health problem or a disease. It is not a substitute for professional care. If you have or suspect you may have a health problem, consult your healthcare provider.