Evaluation of Single-Point Sampling Strategies for the Estimation of Moclobemide Exposure in Depressive Patients

• Published in: Journal of clinical pharmacology 2011-05, Vol.51 (5), p.661-671
• Main Authors: Ignjatovic, Anita Rakic, Miljkovic, Branislava, Todorovic, Dejan, Timotijevic, Ivana, Pokrajac, Milena
• Format: Article
• Language: English
• Subjects: Adult; Antidepressive Agents - administration & dosage; Antidepressive Agents - blood; Antidepressive Agents - pharmacokinetics; Area Under Curve; Depression - blood; Depression - drug therapy; depressive patients; Drug Administration Schedule; Drug Monitoring - methods; Drug Therapy, Combination; Female; Humans; Inpatients; Linear Models; Male; Mean square errors; Middle Aged; Moclobemide; Moclobemide - administration & dosage; Moclobemide - blood; Moclobemide - pharmacokinetics; Models, Biological; Monoamine Oxidase Inhibitors - administration & dosage; Monoamine Oxidase Inhibitors - blood; Monoamine Oxidase Inhibitors - pharmacokinetics; predictive performance; Predictive Value of Tests; Reproducibility of Results; Serbia; single-point sampling strategies; systemic exposure
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/0091270010372105

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 (AUC0–6) 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 AUC0–6. The best estimation of AUC0–6 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.