Effect of menstrual cycle on the pharmacokinetics of enantiomers of ibuprofen

Sandhyarani Guggilla, Ramakrishna Devarakonda, Vr Vobolaboina. Vaagdevi Institute of Pharmaceutical Sciences, Warangal, AP, India.

For several reasons no two individuals can be considered identical and hence individualization of therapy is the current trend in treating the patients.The purpose of this study was to characterize the influence of the menstrual cycle on the pharmacokinetics of ibuprofen in healthy female volunteers.The metabolism of profens involves the stereospecific inversion of the in-active R(-) enantiomer to active S(+) enantiomer together with other potentially stereoselective conjugates and oxidative pathways.

Enrolment of Twelve healthy female volunteers have been included in the study after obtaining written informed consent. The age ranged from 16 to 25 years and weight was from 40 to 60 kg respectively.

Experimental design: 600 mg of IBU (racemic mixture) was given to each subject after overnight fasting with 150 ml water and no food was permitted during the next 4h. Blood samples (6ml) were drawn in to heparinized tubes from cubital vein. A predose blood sample served as an analytical blank. Subsequent blood samples were drawn 0.5, 0.75, 1, 1.5, 2, 3, 5, 8, 12 and 24h after drug administration. The plasma samples were stored at –800 C until HPLC analysis.

The mean C max and (±SD) levels of plasma R(-) ibuprofen are 22.7 (±16.5), 29.4 (±33.7) and 22.0 (± 6.8) for three treatments follicular, ovulatory, and luteal phases respectively. The mean AUC0-∞ and (±SD) levels of plasma R(-) ibuprofen 54.7 (±32.0), 59.2 (±18.9) and 71.5 (± 30.4) are for the three treatments follicular, ovulatory and luteal phases respectively. The mean C max and (±SD) levels of plasma S(+) ibuprofen are 19.9 (±7.35), 25.8 (±13.0) and 21.0 (± 4.07) for three treatments follicular, ovulatory, and luteal phases respectively. The mean AUC0-∞ and (±SD) levels of plasma S(+) ibuprofen 80.6 (±60.1), 76.0 (±36.1) and 84.8 (± 30.0) are for the three treatments follicular, ovulatory and luteal phases respectively.

The present study indicated only the trend that the hormone levels may influence the pharmacokinetic behavior of the two isomers. Alternately a population pharmacokinetic study may be under taken.