Ocular pharmacokinetics of orally administered azithromycin in rabbits.

Azithromycin was orally administered to Dutch-belted rabbits following extracapsular lens extraction in one eye. At various times the animals were sacrificed, and serum and ocular tissues were obtained for drug level determination by HPLC-EC. Following a single dose, peak levels of drug in ocular tissues were measured within 8 hours (cornea > 0.5 micrograms/g [15mg/kg]; > 1.5 micrograms/g [3Omg/kg]). Highest levels were obtained in iris and ciliary body ( > 15 micrograms). Measurable tissue levels persisted for at least 120 hours. Trough levels increased proportionately during drug multiple dose administration. Five days following five daily 15mg/kg doses, corneal levels exceeded 0.5 micrograms/g, and iris and ciliary levels were higher than 15 micrograms/g. Aqueous humor and serum levels were equivalent. Vitreous humor levels, though higher than aqueous humor, were consistently < 1 microgram/ml. Extracapsular cataract extraction did not significantly affect drug uptake.

High-performance liquid chromatographic assay with electrochemical detection for azithromycin in serum and tissues.

High-performance liquid chromatographic methods using reversed-phase chromatography and electrochemical detection have been developed for the quantitation of azithromycin in serum and tissues of laboratory animals and humans. Serum sample preparation involved addition of internal standard, alkalinization, and solvent extraction. Tissue sample preparation involved Polytron homogenization in acetonitrile containing internal standard, evaporation of the supernatant, alkalinization of the residue, and solvent extraction. Serum samples were chromatographed on an alkylphenyl-bonded silica column eluted with pH 6.8-7.2 mobile phase with a dual-electrode coulometric detector operated in the oxidative screen mode. Serum and tissue samples were chromatographed on a gamma RP-1 alumina column with pH 11 mobile phase with a glassy carbon amperometric detector. Recovery of azithromycin was 87% from serum and 85% from tissues. Linear standard curves were prepared in serum over two concentration ranges (0.01-0.20 and 0.20-2.0 micrograms/ml) and in tissues over several concentration ranges (0.1-2, 1-10, 10-100, and 100-1000 micrograms/g). In serum and tissues, intra- and inter-assay precision ranged from 1 to 8% and 4 to 11%, respectively. The tissue assay has been applied to liver, kidney, lung, spleen, muscle, fat, brain, tonsil, lymph nodes, eye, prostate and other urological tissues, and gynecological tissues.

Caffeine and paraxanthine pharmacokinetics in the rabbit: concentration and product inhibition effects.

The disposition of caffeine (C) and its major metabolite paraxanthine (P) have been determined following i.v. bolus dosing both separately and concomitantly to New Zealand White rabbits. Caffeine clearances of 1.52-6.71 ml/min/kg were observed and were suggestive of polymorphism with rapid (type I) and slow (type II) metabolizing subpopulations represented. Type II metabolizers exhibited dose-independent pharmacokinetics for C, while the clearances of type I animals were dose-dependent (lower clearances at higher doses). The P clearances were not dose-dependent. In type I rabbits coadministration of P inhibited C metabolism by as much as 71%. Results were consistent with the hypothesis that at least two forms of cytochrome "P-450" mediate the metabolism of C in the rabbit.