Pharmacokinetics and fate of ³H-trospectomycin sulphate, a novel aminocyclitol antibiotic, in male and female rats

Abstract

1. The pharmacokinetics and fate of ³H-trospectomycin sulphate, a novel aminocyclitol antibiotic, were examined in male and female rats after intramuscular (i.m.), intravenous (i.v.) and subcutaneous (s.c.) dosing.

2. Total radioactivity levels in plasma were associated with unchanged trospectomycin. Two radioactive components were found in urine, one was indistinguishable from trospectomycin and the other was probably a degradation product formed after excretion or during storage rather than a metabolite.

3. The disappearance of drug from plasma followed a biphasic pattern with half lives of 0.3–0.4 h and 45–80 h and a large distribution volume, which indicated some retention of drug by tissues. Clearance rates were within the normal range for glomerular filtration rate, which indicated that the primary process of elimination is filtration of unchanged drug.

4. Excretion was initially rapid (>40% by 4 h) and mainly into urine (faecal excretion <20%). Urinary excretion was significantly larger in males than females but faecal excretion was significantly smaller, so that there was no significant difference in total excretion.

5. The bioavailability following s.c. dosing was only =75% but there were few other biologically significant differences between the routes of administration. Absorption following i.m. and s.c. dosing was rapid.

6. Clearance rate and volume of distribution were higher in males than females. Over the dose range 50–200 mg/kg the pharmacokinetics appeared to be mostly linear.