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Pharmacokinetic interaction between fluoxetine and metoclopramide in healthy volunteers
Author(s) -
Vlase Laurian,
Leucuta Adrian,
Farcau Dorin,
Nanulescu Mircea
Publication year - 2006
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.510
Subject(s) - metoclopramide , pharmacokinetics , fluoxetine , antiemetic , pharmacology , chemistry , plasma concentration , area under the curve , medicine , serotonin , chemotherapy , receptor , vomiting
The pharmacokinetic interaction of fluoxetine with metoclopramide in healthy volunteers was evaluated. A dose of 20 mg metoclopramide in combination with 60 mg fluoxetine was administered to 24 healthy male volunteers in a two treatment study design, separated by 8 days in which the fluoxetine alone was administered as a single p.o. dose daily. Plasma concentrations of metoclopramide were determined during a 24 h period following drug administration. Metoclopramide plasma concentrations were determined by a validated HPLC method. Pharmacokinetic parameters of metoclopramide were calculated using non‐compartmental analysis. In the two periods of treatment, the mean peak plasma concentrations ( C max ) were 44.02 ng/ml (metoclopramide alone) and 62.72 ng/ml (metoclopramide after pre‐treatment with fluoxetine). The times taken to reach C max and t max , were 1.15 h and 1.06 h, respectively. The total areas under the curve ( AUC 0–∞ ) were 312.61 ng.h/ml and 590.62 ng.h/ml, respectively. The half‐life values ( t 1/2 ) were 5.52 h and 8.47 h. Statistically significant differences were observed for both AUC 0–∞ and t 1/2 of metoclopramide when administered alone or after 8 days treatment with fluoxetine. The experimental data demonstrate the pharmacokinetic interaction between fluoxetine and metoclopramide and suggest that the observed interaction may be clinically significant, but its relevance has to be confirmed. Copyright © 2006 John Wiley & Sons, Ltd.