260P Granada Congress and Exhibitions Centre
6th European Congress of Pharmacology (EPHAR 2012)

 

 

The influence of sex on the pharmacokinetic properties of molsidomine prolonged release formulation in healthy human volunteers

J Zoulova1, J Kopecky1, A Polaskova1, D Kholova1, 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

 

Sex differences in pharmacokinetics have been described in many drugs (e.g. Soldin 2009, Schwartz 2003, Harris 1995).

The aim of our study was to find out the sex effects on the pharmacokinetics of coronary vasodilator molsidomine in prolonged release formulation. Molsidomine was given to 15 healthy men (19-45 years, 65-86 kg) and 13 healthy women (24-48 years, 56-75 kg) in a single oral dose of 8 mg (one tablet). Blood samples (9-10 ml) were drawn 0-14 hours after the administration. Plasma molsidomine concentrations were determined by HPLC with UV detection.

Calculated pharmacokinetic parameters are presented in Table 1. Data are given as mean ± standard deviation, except for tmax data, which are given as median and range. Higher values of AUCs and Cmax were found in women. Statistical analysis of logarithmically transformed parameters (t-test) revealed that these differences were significant only in the case of Cmax. Adjustment of Cmax for 70 kg body weight eliminated this significance (Table 2). Higher interindividual variability of pharmacokinetic parameters was found in women.

It seems that sex has only limited effect on the pharmacokinetic properties of molsidomine in prolonged release formulation.

Table 1. Pharmacokinetic parameters of molsidomine after oral administration (dose: 8 mg).

Parameter AUC0-t AUC0-inf Cmax HVD tmax t1/2
[ng.h/ml] [ng.h/ml] [ng/ml] [h] [h] [h]
Men 177± 66 195 ± 64 30 ± 7 5.8 ± 1.5 2.0 (0.33 - 3.0) 3.0 ± 0.5
Women 265 ± 147 286 ± 153 42 ± 15* 5.5 ± 2.0 1.5 (0.33 - 3.0) 2.9 ± 0.7

* p < 0.05; HVD … half value duration (= time span where plasma concentrations are equal to or higher than the half Cmax)

Table 2. Weight-adjusted pharmacokinetic parameters of molsidomine.

Parameter AUC0-t,adj AUC0-inf,adj Cmax,adj
[ng.h/ml] [ng.h/ml] [ng/ml]
Men 191 ± 71 211 ± 69 32 ± 8
Women 245 ± 140 265 ± 147 39 ± 14

References:

Soldin OP, Mattison DR. Sex differences in pharmacokinetics and pharmacodynamics. Clin Pharmacokinet 2009;48:143-57.

Schwartz JB. The influence of sex on pharmacokinetics. Clin Pharmacokinet 2003;42:107-21.

Harris RZ, Benet LZ, Schwartz JB. Gender effects in pharmacokinetics and pharmacodynamics. Drugs 1995;50:222-39.