Effect of Pyrimidine Nucleosides on Body Temperatures of Man and Rabbit in Relation to Pharmacokinetic Data

Godefridus J. Peters, Cees J. van Groeningen, Emile Laurensse, Ineke Kraal, Albert Leyva, Jan Lankelma, Herbert M. Pinedo

Research output: Contribution to journalArticlepeer-review

Abstract

The effect of high-dose uridine on body temperatures of rabbits and man has been studied in relation to plasma concentrations of uridine and its catabolite uracil. Uridine induced fever in both rabbits and man. High-dose cytidine had no influence on body temperature in rabbits. Plasma concentrations of uridine were between 1 and 1.5 m M at 30 min after an iv bolus injection of 400 mg uridine/kg in rabbits and reached peak levels of 2 m M after a 1-hr infusion of 12 g uridine/m2 in man. The plasma concentration of cytidine in rabbits was about 0.5 m M and that of uridine was 0.30 m M at 30 min after an iv bolus injection of 400 mg cytidine/kg. The mean residence time for uridine in patients and rabbits varied between 80 and 195 min. The area under the plasma concentration–time curve (AUC) for uridine in rabbits was 2.0 mmol · hr/liter, and that for cytidine was 0.6 mmol · hr/liter. A large AUC for uridine indicates a prolonged exposure of tissues to uridine, which might lead to extensive formation of degradation products. The administration of some of these catabolites, dihydrouracil (at 20–40 mg/kg), carbamyl-β-alanine (at 60 mg/kg), and β-alanine (at 300–400 mg/kg), resulted in a significant increase in body temperature. It is concluded that the change in body temperature associated with uridine administration was not due to bacterial pyrogens but that one of the degradation products might be involved in thermoregulation.

Original languageEnglish (US)
Pages (from-to)113-119
Number of pages7
JournalPharmaceutical Research
Volume4
Issue number2
DOIs
StatePublished - 1987
Externally publishedYes

Keywords

  • body temperature
  • high-dose uridine
  • uridine catabolites
  • uridine pharmacokinetics

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Organic Chemistry
  • Pharmacology (medical)
  • Pharmaceutical Science
  • Pharmacology
  • Chemistry(all)

Fingerprint

Dive into the research topics of 'Effect of Pyrimidine Nucleosides on Body Temperatures of Man and Rabbit in Relation to Pharmacokinetic Data'. Together they form a unique fingerprint.

Cite this