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

Authorized Users Only
2011
Authors
Rakić-Ignjatović, Anita
Miljković, Branislava
Todorović, Dejan
Timotijević, Ivana
Pokrajac, Milena
Article (Published version)
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Abstract
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 yi...elded 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.

Keywords:
Moclobemide / single-point sampling strategies / systemic exposure / predictive performance / depressive patients
Source:
Journal of Clinical Pharmacology, 2011, 51, 5, 661-671
Publisher:
  • Wiley, Hoboken
Projects:
  • Eksperimentalna i kliničko-farmakološka istraživanja mehanizma dejstva i interakcija lekova u nervnom i kardiovaskularnom sistemu (RS-145001)

DOI: 10.1177/0091270010372105

ISSN: 0091-2700

PubMed: 20495135

WoS: 000289942400005

Scopus: 2-s2.0-79955541937
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URI
http://farfar.pharmacy.bg.ac.rs/handle/123456789/1518
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Institution
Pharmacy

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