Evaluation of single-point sampling strategies for the estimation of moclobemide exposure in depressive patients.
Because moclobemide pharmacokinetics vary considerably among individuals, monitoring of plasma concentrations lends insight into its pharmacokinetic behavior and enhances its rational use in clinical practice. The aim of this study was to evaluate whether single concentration-time points could adequately predict moclobemide systemic exposure. Pharmacokinetic data (full 7-point pharmacokinetic profiles), obtained from 21 depressive inpatients receiving moclobemide (150 mg 3 times daily), were randomly split into development (n = 18) and validation (n = 16) sets. Correlations between the single concentration-time points and the area under the concentration-time curve within a 6-hour dosing interval at steady-state (AUC(0-6)) were assessed by linear regression analyses. The predictive performance of single-point sampling strategies was evaluated in the validation set by mean prediction error, mean absolute error, and root mean square error. Plasma concentrations in the absorption phase yielded unsatisfactory predictions of moclobemide AUC(0-6). The best estimation of AUC(0-6) was achieved from concentrations at 4 and 6 hours following dosing. As the most reliable surrogate for moclobemide systemic exposure, concentrations at 4 and 6 hours should be used instead of predose trough concentrations as an indicator of between-patient variability and a guide for dose adjustments in specific clinical situations.
Ignjatovic
Anita Rakic
AR
Medicines and Medical Devices Agency of Serbia, Vojvode Stepe No. 458, Belgrade 11152, Serbia. anitarakic@beotel.net
Miljkovic
Branislava
B
Todorovic
Dejan
D
Timotijevic
Ivana
I
Pokrajac
Milena
M
D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003863:Depression / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007297:Inpatients; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020912:Moclobemide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008954:Models, Biological; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D055771:Serbia
D000928:Antidepressive Agents; D008996:Monoamine Oxidase Inhibitors; D020912:Moclobemide