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Evaluation of Single‐Point Sampling Strategies for the Estimation of Moclobemide Exposure in Depressive Patients
Author(s) -
Ignjatovic Anita Rakic,
Miljkovic Branislava,
Todorovic Dejan,
Timotijevic Ivana,
Pokrajac Milena
Publication year - 2011
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270010372105
Subject(s) - moclobemide , dosing , pharmacokinetics , confidence interval , medicine , pharmacology , statistics , mathematics , hippocampus , antidepressant
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.