The effects of peptidoglycan, a pyrogenic constituent of gram-positive microorganisms, on the pharmacokinetics of rifampicin.
Pharmacokinetics of rifampicin (20 mg/kg orally or i.v.) was determined in calves and rabbits. Seven days later a model pyrogen was administered i.v. to the same animals and 1 hr later the rifampicin administration was repeated. The pharmacokinetic analysis of oral rifampicin was performed using a one-compartment open model with absorption. Intravenously administered rifampicin was analysed by a two-compartment intravascular model. Injection of peptidoglycan in pyrogenic doses led to a significant increase of orally applied rifampicin serum levels in both animal species. The i.v. administration of rifampicin had the same parameters in the control and peptidoglycan experiments. Daily pretreatment of rabbits with small doses of peptidoglycan induced tolerance to the pyrogenic effect. In tolerant animals we did not observe any changes of rifampicin serum levels. Elevated temperature alone was not responsible for observed pharmacokinetic changes leading to the increase of bioavailability of oral rifampicin since another pyrogenic substance (endotoxin) had an opposite effect on pharmacokinetics of previously tested drugs.
Lavický
J
J
Department of Pharmacology, Faculty of Paediatric Medicine, Prague, Czechoslovakia.
Urbanová
Z
Z
Rasková
H
H
Rotta
J
J
Vanĕcek
J
J
D000284:Administration, Oral; D000818:Animals; D002417:Cattle; D002682:Chinchilla; D005334:Fever / Q000139:chemically induced; D006094:Gram-Positive Bacteria / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D010457:Peptidoglycan / Q000096:biosynthesis / Q000494:pharmacology*; D011749:Pyrogens / Q000096:biosynthesis / Q000494:pharmacology*; D011817:Rabbits; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics*
D010457:Peptidoglycan; D011749:Pyrogens; D012293:Rifampin