title: Simplification of therapeutic drug monitoring for twice-daily regimens of lopinavir/ritonavir for HIV infection.
abstract: Cost and inconvenience limit the application of full 12-hour pharmacokinetic (PK) analysis for routine therapeutic drug monitoring of antiretroviral medications. We explore whether lopinavir (LPV) and ritonavir (RTV) 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 AUC0-12 h 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 postdose emerged from this analysis.
authors.affiliation: British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada. calexan@hivnet.ubc.ca
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Alexander
authors.forename: Julio S G
authors.initials: JS
authors.lastname: Montaner
authors.forename: Jérôme J
authors.initials: JJ
authors.lastname: Asselin
authors.forename: Lillian
authors.initials: L
authors.lastname: Ting
authors.forename: Kelly
authors.initials: K
authors.lastname: McNabb
authors.forename: Marianne
authors.initials: M
authors.lastname: Harris
authors.forename: Silvia
authors.initials: S
authors.lastname: Guillemi
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
mesh_terms: D000328:Adult; D019540:Area Under Curve; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir