Analysis of amifloxacin in plasma and urine by high-pressure liquid chromatography and intravenous pharmacokinetics in rhesus monkeys.

An analytical method for the quantitation of amifloxacin, 6-fluoro-1,4-dihydro-1-(methylamino)-7-(4-methyl-1-piperazinyl)-4-oxo-3- quinolinecarboxylic acid, in plasma and urine has been developed. The method involves extraction with chloroform, back-extraction into 0.1 M sodium hydroxide, and subsequent analysis by reverse-phase high-pressure liquid chromatography with UV detection. The precision of the assay calculated as the overall standard deviation was +/- 4.9% in plasma and +/- 1.1% in urine. The range of mean percent differences from the nominal values was used as an estimate of accuracy and was 93.6 to 103% of the nominal values in plasma and 95.2 to 107% of the nominal values in urine. The minimum quantifiable levels were 0.032 micrograms/ml in plasma and 2.7 micrograms/ml in urine. The methods were employed in a pharmacokinetic analysis of amifloxacin after intravenous administration to rhesus monkeys. The decline in drug plasma levels was described by a biexponential process with mean rates of 8.4 h-1 and 0.32 h-1 with corresponding half-lives of ca. 5 min and 2.2 h. Amifloxacin was rapidly excreted, with ca. 53% of the dose appearing in the urine within 48 h after medication. The mean renal clearance +/- standard deviation was 4.4 +/- 1.0 ml X kg-1 X min-1 and is compatible with passive glomerular filtration in this species.