Pharmacokinetics and Bioequivalence Study of Doxycycline Capsules in Healthy Male Subjects

The aim of the present study was to compare the bioavailability of doxycycline (CAS 564-25-0) from two different doxycycline hyclate (CAS 24390-14-5) capsules (Monodoks © 100 mg capsule as test preparation and 100 mg capsule of the originator product as reference preparation) in 24 healthy male subjects. The study was conducted according to an open-label, randomised two-period cross-over design with a wash-out phase of 16 days. Blood samples for pharmacokinetic profiling were taken up to 72 h post-dose, and doxycycline plasma concentrations were determined with a validated HPLC method with UV-detection. Maximum plasma concentrations (C max ) of 1,715.1 ng/ml (test) and 1,613.3 ng/ml (reference) were achieved. Areas under the plasma concentration-time curve (AUC 0→∞ )of 28,586.5 ng · h/ml (test) and 29,047.5 ng · h/ml (reference) were calculated. The median t max was 1.88 h (test) and 2.00 h (reference). Plasma elimination half-lives (t 1/2 ) of 16.49 h (test) and 16.75 h (reference) were determined. Both primary target parameters AUC 0→∞ and C max were tested parametrically by analysis of variance (ANOVA) and the 90% confidence intervals were between 92.39%-l03.53% (AUC 0→∞ ) and 98.45%-111.74% (C max ). Bioequivalence betweer test and reference preparation was demonstrated since for both parameters AUC and C max the 90% confidence intervals of the T/R ratios of logarithmically transformed data were in the generally accepted range of 80%-l25 %.