|
|
|
Share this Poster with a Colleague
Background: ABT-378 is a potent HIV protease inhibitor (PI), with favorable pharmacokinetics allowing twice daily (BID) dosing. It has shown excellent antiviral activity in antiretroviral naïve patients. ABT-378 is metabolized by CYP3A. Ritonavir is metabolized by CYP3A and to a lesser extent by CYP2D6. The metabolism of ABT-378 is highly inhibited by ritonavir. The ERMBT is often used to characterize individual hepatic CYP3A activity. The potential for ERMBT serving as a predictor for ABT-378 and ritonavir exposures was assessed in an interaction study with nevirapine(NVP).
Methods: Group (gp) A received 400/100mg ABT-378/ritonavir(A/r) bid on days 1-20, gp B received 200mg NVP qd on days 1-14 and 200mg NVP bid on days 15-20, and gp C received 400/100mg A/r bid on days 1-20 plus 200mg NVP qd on days 1-14, and 200mg NVP bid on days 15-20. The ERMBT was performed during screening and on day 22. ABT-378, ritonavir, and NVP plasma concentrations were determined on days 14 and 20.
Results: Essentially no correlation was found between the results of ERMBT and the area under the plasma concentration-time curve(AUC) of ABT-378 and ritonavir for gps A and C. The AUC of NVP in the NVP-alone gp B was correlated with ERMBT results (r2: 0.56 to 0.83, p=0.012 - 0.02). The correlation between the ERMBT results and the AUC of ABT-378, ritonavir, and NVP were poor for gp C.
Conclusions: These results indicate the ABT-378 and ritonavir exposures are not correlated with hepatic CYP3A activity. Thus, ERMBT cannot be used to predict the exposures for ABT-378 and ritonavir. Similar results have been reported with ERMBT for other PIs, such as nelfinavir and indinavir. Although the exposures of NVP appeared to be reasonably well correlated with the results of ERMBT when NVP was used alone, the correlation was not present when NVP was used with ABT-378 and ritonavir.
Abstract prepared by Abbott Laboratories
From the 39th ICAAC
 Main
New/Newsworthy
|
Kaletra Conference Data |
Home |
|
ABT-378
and Ritonavir Exposures Are Not Predicted by Erythromycin Breath Test (ERMBT) |
