Pharmacokinetics of trospectomycin sulphate in healthy subjects after single intravenous and intramuscular doses.

The pharmacokinetics of trospectomycin (75-1000 mg free base equivalents) were studied in 128 healthy males (eight per dose group), after a 20 min intravenous (i.v.) infusion and intramuscular (i.m.) injection of trospectomycin sulphate. The concentrations of trospectomycin in serum were described by bi- or tri-exponential disposition functions indicating an initial half-life of 1.1-1.4 h for the i.v. dose and 1.6-2.1 h for the i.m. dose and terminal half-lives of over 15 h. Most of the drug was eliminated rapidly (mean residence time 5-12 h). The distribution volume was 59-112% of body weight and clearance was 112-152 ml min-1. The absorption into blood after i.m. dosing was rapid. The area under the concentration-time curve and maximum concentration values were linearly related to dose. Serum drug concentrations fell below the minimum inhibitory concentration values for a variety of organisms by 8-12 h, which indicates that two or three times daily dosing would be appropriate. However, the long terminal half-life suggests that significant accumulation is likely in some tissues with an 8 h dose interval and this may prolong the action of trospectomycin.