Markov Model for Characterizing Neuropsychologic Impairment and Monte Carlo Simulation for Optimizing Efavirenz Therapy
| dc.contributor.author | Bisaso Kuteesa, Ronald | |
| dc.contributor.author | Mukonzo, Jackson K. | |
| dc.contributor.author | Ette, Ene I. | |
| dc.date.accessioned | 2022-12-04T13:41:24Z | |
| dc.date.available | 2022-12-04T13:41:24Z | |
| dc.date.issued | 2015 | |
| dc.description.abstract | The study was undertaken to develop a pharmacokinetic-pharmacodynamic model to characterize efavirenz-induced neuropsychologic impairment, given preexistent impairment, which can be used for the optimization of efavirenz therapy via Monte Carlo simulations. The modeling was performed with NONMEM 7.2. A 1-compartment pharmacokinetic model was fitted to efavirenz concentration data from 196 Ugandan patients treated with a 600-mg daily efavirenz dose. Pharmacokinetic parameters and area under the curve (AUC) were derived. Neuropsychologic evaluation of the patients was done at baseline and in week 2 of antiretroviral therapy. A discrete-time 2-state first-order Markov model was developed to describe neuropsychologic impairment. Efavirenz AUC, day 3 efavirenz trough concentration, and female sex increased the probability (P01) of neuropsychologic impairment. Efavirenz oral clearance (CL/F) increased the probability (P10) of resolution of preexistent neuropsychologic impairment. The predictive performance of the reduced (final) model, given the data, incorporating AUC on P01and CL /F on P10, showed that the model adequately characterized the neuropsychologic impairment observed with efavirenz therapy. Simulations with the developed model predicted a 7% overall reduction in neuropsychologic impairment probability at 450 mg of efavirenz. We recommend a reduction in efavirenz dose from 600 to 450 mg, because the 450-mg dose has been shown to produce sustained antiretroviral efficacy | en_US |
| dc.identifier.citation | Bisaso, K. R., Mukonzo, J. K., & Ette, E. I. (2015). Markov model for characterizing neuropsychologic impairment and Monte Carlo simulation for optimizing efavirenz therapy. The Journal of Clinical Pharmacology, 55(11), 1229-1235.DOI: 10.1002/jcph.533 | en_US |
| dc.identifier.other | DOI: 10.1002/jcph.533 | |
| dc.identifier.uri | https://nru.uncst.go.ug/handle/123456789/5834 | |
| dc.language.iso | en | en_US |
| dc.publisher | The Journal of Clinical Pharmacology | en_US |
| dc.subject | Markov model | en_US |
| dc.subject | efavirenz | en_US |
| dc.subject | neuropsychologic impairment | en_US |
| dc.subject | NONMEM | en_US |
| dc.subject | Monte Carlo simulation | en_US |
| dc.title | Markov Model for Characterizing Neuropsychologic Impairment and Monte Carlo Simulation for Optimizing Efavirenz Therapy | en_US |
| dc.type | Article | en_US |