265P Granada Congress and Exhibitions Centre
6th European Congress of Pharmacology (EPHAR 2012)

 

 

The influence of sex on pharmacokinetics of isosorbide-5-mononitrate in healthy human volunteers

I Zubata1, L Vyslouzil1, J Kopecky1, J Pastera1, J Chladek1, K Macek2, J Kvetina1. 1Institute of Experimental Biopharmaceutics, Joint Research Centre of PRO.MED.CS Praha a.s. & Academy of Sciences of the Czech Republic, Hradec Kralove, CZ-50003, Czech Republic, 2University Hospital, Hradec Kralove, CZ-50005, Czech Republic

 

Although sex-related disparity in pharmacokinetics has been identified for numerous drugs, differences are generally only subtle. Sex-based factors that affect pharmacokinetics include drug-metabolising enzymes, drug transporters, gastric motility, excretion activity and body composition (body weight, plasma volume, percent of body fat and organ blood flow).

The aim of our study was to evaluate effects of gender on pharmacokinetic parameters of isosorbide-5-mononitrate (IS-5-MN). IS-5-MN was given to 14 healthy men (24 ± 6 years, 77 ± 11 kg) and 10 healthy women (38 ± 9 years, 65 ± 10 kg) in a single oral dose of 40 mg. Blood samples (10 ml) were drawn up to 32 hours after the administration. Plasma IS-5-MN concentrations were determined by gas chromatography.

Table. Pharmacokinetic parameters of IS-5-MN after a single oral dose of 40 mg

Parameter AUC0-32 AUC0- ∞ Cmax tmax t1/2
[µg.h/ml] [µg.h/ml] [µg/ml] [h] [h]
Men 6.56 ± 1.05 6.73 ± 1.04 1.11 ± 0.34 0.57 ± 0.40 6.22 ± 1.35
Women 8.45 ± 1.52* 8.54 ± 1.55* 1.25 ± 0.22 0.72 ± 0.40 4.74 ± 0.57*

Mean ± SD, * p < 0.05

Statistical analysis of parameters revealed significant differences between men and women. However, the differences in AUCs were no longer significant after adjusting for potential confounder (body weight). Thus, it seems that gender has no influence on the rate and extent of absorption of isosorbide-5-mononitrate.