[Determination of bifonazole using HPLC in pharmacokinetic studies]. / Opredelenie bifonazola metodom VEZhKh pri farmakokineticheskikh issledovaniiakh.

A sensitive method for HPLC quantification of bifonazole, an antimycotic drug, in the skin and plasma was developed. The skin samples were homogenized with the use of a physiological solution (1:5) and then centrifuged at 2000 r.p.m. for 20 minutes. Bifonazole was extracted from the homogenates or plasma with methylene chloride. The organic phase was evaporated to dryness under nitrogen at 45 degrees C, the residue was redissolved in methanol and an aliquot of 0.03 ml was injected to the HPLC system for determination of the drug content. A Silasorb C column (30 cm x 4.6 mm, 10 microns) was used. The mobile phase consisted of acetonitrile, 0.12 M sodium acetate and methanol (84:15:1). The flow rate was 1.5 ml/min. The UV absorption was monitored at lambda 254 nm. The calibration plots were linear within the concentration ranges of 1 to 20 micrograms/g. The determination limit was 0.02 microgram/g. The bifonazole pharmacokinetics was studied with the developed method on rats after a single application of 1 per cent drug cream to the skin. The cream was manufactured by two different companies (formulations A and B). The skin and blood samples were collected 0.5, 1, 2, 6, 24 and 48 hours after the bifonazole cream application in a dose of 1 g/kg. The plasma levels of bifonazole were below the detection limit of the method throughout the observation period whereas the skin concentrations could be measured within 0.5-48 hours. Despite the faster skin penetration of bifonazole applied as formulation A the relative extent of the penetration was close to 1 (0.95) and the mean residence times were similar (14.9 and 14.5 hours for formulations A and B respectively). The developed analytical procedure is useful in pharmacokinetic studies with bifonazole.

[Correlation between pharmacokinetic parameters of rifampicin and its biologically active metabolite as related to estimation of the relative bioavailability of the antibiotic]. / Vzaimosviaz' mezhdu parametrami farmakokinetiki rifampitsina i ego biologicheski aktivnogo metabolita v kontekste otsenki otnositel'noi biodostupnosti antibiotika.

In the bioavailability studies with drugs biotransformed to biologically active metabolities only the concentrations of the parent drug (PD) are usually taken into account even when the pharmacokinetic data on the metabolite(s) (M) are available. However, such data may be useful as an alternative source for the bioavailability determination. Moreover, the clinical outcomes often depend on both the PD and M concentrations. The aim of the study performed with two rifampicin formulations, tablets and dragee, was to correlate the pharmacokinetic parameters of the PD and 25-O-deacetylrifampicin, a microbiologically active M of rifampicin, and to examine whether the bioavailability parameters based on the PD and M concentrations were compatible. The serum concentrations of the PD and M were determined in 8 healthy volunteers by HPLC. Despite different patterns of the PD and M pharmacokinetic profiles the PD peak concentration (Cmax) and especially the AUC correlated with Cmax or the AUC of the M (r = 0.76 and 0.92 respectively). Moreover, the extent of the absorption expressed as the AUC ratio for the PD correlated with the AUC ratio for the M (r = 0.86). However, neither the time to reach the maximum (tmax), nor the Cmax/AUC ratio, a measure of the absorption rate, based on the PD pharmacokinetic data correlated with the respective parameters calculated with using the M concentrations. Thus, only the estimates of the extent of the absorption and not of the absorption rate based on the PD and M data may be considered as compatible.