Simplification of Therapeutic Drug Monitoring for Twice-Daily Regimens of Lopinavir/Ritonavir

Cost and inconvenience limit the application of full 12-hour pharmacokinetic (PK) analysis for routine therapeutic drug monitoring (TDM) of antiretroviral medications. Canadian researchers explored whether lopinavir/ LPV and ritonavir/ RTV (Norvir) exposures can be estimated with limited sampling for patients taking twice-daily LPV/RTV.

One hundred and one PK profiles from 81 patients, most receiving salvage therapies including twice-daily LPV/RTV, were obtained for the analysis.

After a minimum of 2 weeks on a stable regimen, blood was drawn immediately before and at 1, 2, 4, 6, 8, 10, and 12 hours after a timed medication dose. Plasma drug concentrations were determined by a validated HPLC-MS-MS assay.

Peak concentrations, evening troughs, and AUC0-12h were entered into linear and log10-log10 linear regression models to determine the best correlation with LPV and RTV plasma concentrations using a maximum of 2 time points.

The accuracy and precision of PK parameter estimates of the resultant models were tested on data collected for an additional 25 patients. Twelve models using various combinations of 2 timed LPV concentrations afforded accurate (maximum % bias = -6.45) and precise (relative standard deviation < 15%) estimates for the LPV peak concentration or AUC0-12h.

Four sets of 2 concentrations provided simultaneous estimates of both PK parameters, with the best estimates derived from data collected at 2 and 6 hours postdose.

Evening trough concentrations were the best estimators of the daily nadir; however, no adequate substitute for collecting blood 12 hours post-dose emerged from this analysis.

British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada; and University of British Columbia, Faculty of Medicine, Department of Medicine, Vancouver, British Columbia, Canada.

10/04/04