[TuPe3.1B08] Pharmacokinetics of SCH 417690 Administered Alone or in Combination with Ritonavir and Efavirenz in Healthy Volunteers

3rd International AIDS Society Conference on HIV Pathogenesis and Treatment

Rio de Janeiro - July 24 - 27, 2005

PHARMACOKINETICS OF SCH 417690 ADMINISTERED ALONE OR IN COMBINATION WITH RITONAVIR AND EFAVIRENZ IN HEALTHY VOLUNTEERS

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. TuPe3.1B08

Saltzman M.¹, Rosenberg M.¹, Kraan M.², Keung A.², Boutros T.³, Soni P.², Sansone A.²
¹Parkway Research Center, Inc., North Miami Beach, FL, United States of America, ²Schering Plough Research Institute, Kenilworth, New Jersey, United States of America, ³Pfizer, Inc., San Diego, CA, United States of America

INTRODUCTION: SCH 417690, a novel CCR5 receptor antagonist, is metabolized by CYP3A4 and is known to demonstrate boosted exposure with ritonavir. This study assessed the effect of ritonavir (a CYP3A4 inhibitor) plus efavirenz (a CYP3A4 inducer) administration on SCH 417690 pharmacokinetics.

METHODS: In this randomized, open-label study healthy adults received (A) SCH 417690 10 mg alone, (B) SCH 417690 10 mg + ritonavir 100 mg, (C) SCH 417690 10 mg + efavirenz 600 mg , or (D) SCH 417690 10 mg + ritonavir + efavirenz QD for 14 days. Blood samples were obtained before and at multiple time points after dosing on Days 1 and 14. Pharmacokinetic end points were C_max and AUC_0-12, analyzed using a 1-way ANOVA. Safety was assessed using adverse events (AE), vital signs, electrocardiograms, and laboratory values.

RESULTS: Thirty-six subjects enrolled (median age, 39 yrs; 78% men; 81% white), and completed the study. SCH 417690 exposure was significantly increased by ritonavir (AUC, +582% [90% CI, 422% to 801%]; C_max, +278% [208% to 371%]), while exposure was significantly reduced by efavirenz (AUC, -81% [-74% to -86%]; C_max, -67% [-56% to -75%]). Coadministration of ritonavir plus efavirenz with SCH 417690 resulted in a statistically significant increase in SCH 417690 exposure (AUC, +384% [279% to 529%]; C_max, +196% [147% to 261%]) compared with SCH 417690 alone. Overall, 39% of subjects reported ≥1 AE. Mild to moderate dizziness and headache possibly related to study treatment were the most common AEs. Vital signs, ECGs, and laboratory tests were unremarkable.

CONCLUSIONS: SCH 417690, administered with ritonavir and/or efavirenz, was well tolerated. Coadministration of ritonavir plus efavirenz with SCH 417690 increased SCH 417690 exposure significantly, albeit not as much as with ritonavir alone, suggesting that a CYP3A4 inhibitor has a greater effect than a CYP3A4 inducer on SCH 417690 exposure, when given in combination for 14 days.

Download PDF of this abstract.

050724
Basic | TuPe3.1B08 | Angela Sansone
PK and pharmacodynamics

Copyright © 2005 - International AIDS Society (IAS). All information and content relating to the abstracts from the 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment, such as text, graphics, logos, button icons, images, audio clips, and software is protected by copyright. Permission is hereby granted for the non-commercial use or reproduction of the information on this web site, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.

AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2005. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2005. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. Permission is hereby granted for the non-commercial use or reproduction of the information herein, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.