259P Granada Congress and Exhibitions Centre
6th European Congress of Pharmacology (EPHAR 2012)

 

 

The influence of sex on the pharmacokinetics of molsidomine in healthy human volunteers

J Kopecky1, J Zoulova1, A Polaskova1, D Kholova1, K Macek2, J Chladek1, J Kvetina1. 1Institute of Exp. Biopharmaceutics, Joint Research Centre of PRO.MED.CS Praha a.s. & Academy of Sciences of the Czech Republic, Hradec Kralove, CZ-50003, Czech Republic, 22nd Department of Internal Medicine, University Hospital, Hradec Kralove, CZ-50005, Czech Republic

 

Sex differences in pharmacokinetics have been described in many drugs (Soldin OP et al., Clin Pharmacokinet 2009; 48: 143-57; Schwartz JB, Clin Pharmacokinet 2003; 42: 107-21).

The aim of our study was to find out the influence of sex on the pharmacokinetics of NO-donor molsidomine.

Molsidomine was administered to 12 healthy men (18-43 years, 70-92 kg) and 12 healthy women (25-51 years, 53-85 kg) in a single oral dose of 4 mg (one immediate release tablet). The subjects were fasting 10 hours before molsidomine administration. Blood samples (10 ml) were drawn
0-10 hours after the administration. Plasma molsidomine concentrations were determined by HPLC with UV detection. Calculated pharmacokinetic parameters (arithmetic mean ± standard deviation, except for tmax data which are given as median and range) are presented in the Table. Unpaired
t-test was used for statistical evaluation of logarithmically transformed pharmacokinetic parameters (men versus women).

Table. Pharmacokinetic parameters of molsidomine after oral administration (dose: 4 mg).

Parameter Unit Men Women p
AUCinf [ng.h/ml] 84.6 ± 29.2 156.1 ± 72.9 0.0017
AUClast [ng.h/ml] 75.4 ± 28.1 145.0 ± 66.1 0.0011
Cmax [ng/ml] 34.2 ± 13.1 50.7 ± 16.2 0.0087
tmax [min] 20 (20-60) 30 (20-90) -
t1/2 [h] 1.71 ± 0.29 1.81 ± 0.62 0.6540
AUCinf, adj [ng.h/ml] 94.2 ± 32.1 141.9 ± 69.9 0.0438
AUClast, adj [ng.h/ml] 83.9 ± 30.9 131.7 ± 63.0 0.0248
Cmax, adj [ng/ml] 38.2 ± 14.9 45.6 ± 15.8 0.1800

adj … body weight-adjusted parameter (calculated by normalizing for 70 kg of body weight)

There were statistically significant differences between men and women in the parameters AUCs and Cmax. Significant differences between men and women in AUCs, but not in Cmax, were found even after adjustment of these parameters to the body weight. Thus, the pharmacokinetics of molsidomine is influenced by the sex in healthy human volunteers. Different body weight in men and women does not seem to be the only one reason for these differences (at least in AUCs).