Pharmacokinetics and fate of 3H-trospectomycin sulphate, a novel aminocyclitol antibiotic, in male and female rats.
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 (greater than 40% by 4 h) and mainly into urine (faecal excretion greater than 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 approximately 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.
Nichols
D J
DJ
Drug Investigation and Clinical Research, Upjohn Ltd., Crawley, West Sussex, UK.
Burrows
M
M
Bye
A
A
Constable
D A
DA
Dring
L G
LG
Jeffrey
P
P
D000818:Animals; D001682:Biological Availability; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D005243:Feces / Q000737:chemistry; D005260:Female; D006207:Half-Life; D006868:Hydrolysis; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D000198:Spectinomycin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics
C043267:trospectomycin; D000198:Spectinomycin