Pharmacokinetics of levofloxacin in comparison to the racemic mixture of ofloxacin in man

Abstract

After oral administration of a single dose of 200 mg of levofloxacin and 400 mg racemic mixture of ofloxacin to 6 healthy male volunteers in a double-blind, randomised cross-over study, concentrations of the unchanged isomers were determined at various times in serum and urine, over 28 hours and 48 hours, respectively. Each dosing was followed by a wash-out period of one week. Ofloxacin concentrations were determined using an enantioselective and a non-enantioselective high pressure liquid chromatography (HPLC) assay. The two measurements obtained were compared by linear distribution independent regression, and were found to be equivalent. Maximum serum concentration (Cmax) of levofloxacin after the administration of 200 mg of the levo-isomer was 2.42 mg/l (chiral derivatization HPLC, mean values); the corresponding area under the serum concentration-time curve (AUC0-28) was 17.0 mg x h/l. The corresponding Cmax values after the administration of 400 mg (+/-)-isomer (chiral derivatization HPLC and reversed phased HPLC, mean values) were 2.05 mg/l, 1.98 mg/l and 4.41 mg/l for (-)-, (+)- and (+/-) isomer, respectively. The AUCS0-28 were 17.0, 14.6 and 32.7 mg x h/l, respectively. The pharmacokinetics of the (-)- and (+)-isomer were shown to be almost equal. In serum and urine no reracemisation of the (-)-isomer to a racemic mixture was observed. General tolerability was good; no side effects were reported.