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Current Topics in Pharmacology   Volumes    Volume 20 
Abstract
Influence of food and sex on the pharmacokinetics and pharmacodynamics of furosemide
Laura Magallanes, Pietro Fagiolino, Marta Vázquez, Nikoletta Fotaki, Manuel Ibarra, Marianela Lorier, Virginia Bértola, Anna Barindelli
Pages: 45 - 56
Number of pages: 12
Current Topics in Pharmacology
Volume 20 

Copyright © 2016 Research Trends. All rights reserved

ABSTRACT
 
The goal of this study was to investigate if food coadministration might change the pharmacokinetic and the pharmacodynamic responses of a 40-mg oral dose of furosemide in a similar way in male and female subjects. Twelve healthy Caucasian (8 women and 4 men) subjects that participated in a previous bioequivalence study under fasting condition, now received the same two oral formulations [Lasix® (Reference, R) and Furosemide EFA® (Test, T)] with food. Urinary excretion of unchanged drug (PK), and of chloride, sodium and potassium (PD) was monitored throughout time. PK and PD parameters were calculated from the respective excretion rate versus time curve. Since one of the volunteers (woman) abandoned the trial, ten subjects were retained for bioequivalence evaluation in order to maintain the TR/RT sequences of administration balanced. The furosemide excretion rates were significantly reduced in both formulations, but to a higher extent in men, whereas the chloride excretion rate was reduced similarly in both women and men after food coadministration. Sex-related differences in the relative bioavailability between the two formulations obtained after fasting state were overridden when furosemide formulations were coadministered with food. Food intake yielded similar gastric emptying in both sexes. Technological differences between the formulations could not be evidenced under fed condition. Physiological changes are evident not only in the luminal space of the gastrointestinal tract after the ingestion of food, but also in the cardiovascular system, showing intensive blood flow fraction redistribution among the organs. As the subjects were maintained in a resting state during the administration of the formulations both under fast and fed conditions, the increased blood flow fraction destined to the splanchnic region might have come from the renal region, and thereafter, the furosemide renal excretion and its saluretic effect diminished because of food ingestion. These hemodynamic changes could have had a higher impact on males since their renal blood flow fraction is normally higher in comparison with female subjects under fasting conditions.
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