Pharmacokinetics and elimination of moxifloxacin after oral and intravenous administration in man

Abstract

The pharmacokinetics of moxifloxacin and its metabolites M1 (sulpho-compound) and M2 (acyl-glucuronide) were characterized in 12 healthy male volunteers in an open, randomized, crossover study. After an overnight fast the volunteers were given a single 400 mg dosage of moxifloxacin either as a tablet or a 1 h infusion with a washout phase of at least 1 week between the two treatments. Multiple plasma, faeces and urine samples were collected for the analysis of moxifloxacin and metabolites using validated HPLC with fluorescence detection. The AUC for both formulations was comparable with bioequivalence criteria fulfilled, with C_max after oral treatment approximately 31% lower. Following oral administration, absorption was fast with low to medium variability (mean dissolution and absorption time 2.4 h). The absolute bioavailability was 86%. The excretion of moxifloxacin and its metabolites was quantified in a subset of eight subjects. More than 96% of the dose was recovered from urine and faeces after oral dosing, and >98% following iv administration of the drug. M1, which is strongly bound to plasma proteins (90%), was mainly eliminated into faeces (approximately 37–38% of the administered dose) and to a minor extent into urine (2.5% of the administered dose) by active tubular secretion. M2 (only 5% bound to plasma protein) was only found in urine, where it amounted to approximately 14% of the dose. Plasma concentrations of the metabolites were much lower than those of the parent compound. Moxifloxacin was well tolerated with few adverse events and no clinically relevant changes in laboratory values.