Nonlinear pharmacokinetics of 5-fluorouracil in rats

Journal of Pharmaceutical Sciences
V R JarugulaF D Boudinot

Abstract

The effects of dose on the pharmacokinetics of 5-fluorouracil (5-FU) were investigated following intravenous administration of 5-FU at 10, 50, and 100 mg/kg to adult male Sprague-Dawley rats. Six rats were studied at each dose level. The dose-normalized area under the curve (AUC) was significantly higher after administration of 100 mg/kg (1.14 +/- 0.55 mg.h/L/mg; mean +/- SD) than after 50 mg/kg (0.50 +/- 0.18 mg.h/L/mg) or 10 mg/kg (0.43 +/- 0.11 mg.h/L/mg), indicating nonlinear elimination of 5-FU in rats. Dose- and time-average pharmacokinetic parameters were calculated by area/moment analysis. The systemic clearance of 5-FU following administration of 100 mg/kg was significantly lower (1.1 +/- 0.49 L/h/kg) than after 50 mg/kg (2.2 +/- 0.72 L/h/kg) or 10 mg/kg (2.4 +/- 0.67 L/h/kg). There was no significant difference in renal clearance values between the three doses (0.47 +/- 0.26 L/h/kg). However, nonrenal clearance was significantly lower after the 100-mg/kg dose (0.77 +/- 0.2 L/h/kg) than after the 50-mg/kg (1.65 +/- 0.49 L/h/kg) and 10-mg/kg (1.87 +/- 0.75 L/h/kg) doses. There was no significant difference between the steady-state volume of distribution values (0.91 +/- 0.36 L/kg) at the three doses. The lower nonrenal ...Continue Reading

References

May 22, 1975·The New England Journal of Medicine·B A ChabnerD G Johns
Apr 1, 1978·Journal of Pharmacokinetics and Biopharmaceutics·K YamaokaT Uno
Jul 1, 1989·Journal of Pharmaceutical Sciences·B A PatelF D Boudinot
Jun 1, 1983·Computer Programs in Biomedicine·M L Rocci, W J Jusko
Dec 1, 1980·Cancer Treatment Reviews·M A Friedman, R J Ignoffo
Jun 1, 1983·Journal of Pharmaceutical Sciences·L A CelioA J Piraino
May 1, 1980·Acta Pharmacologica Et Toxicologica·O E AlmersjöP Wåhlén
Aug 1, 1980·Clinical Pharmacology and Therapeutics·J M CollinsC E Myers
Dec 1, 1980·Journal of Pharmaceutical Sciences·T A PhillipsP G Welling
Feb 23, 1996·Journal of Chromatography. B, Biomedical Applications·V R Jarugula, F D Boudinot
Sep 1, 1964·Clinical Pharmacology and Therapeutics·B CLARKSOND HUTCHISON
Nov 1, 1961·Annals of Internal Medicine·B J KENNEDY, A THEOLOGIDES

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Citations

Nov 12, 1998·The Journal of Pharmacy and Pharmacology·H YuasaJ Watanabe
Sep 27, 2013·Journal of Translational Medicine·Chen-Hsi HsiehYu-Jen Chen
Mar 27, 2010·Journal of Translational Medicine·Chen-Hsi HsiehYu-Jen Chen
Oct 28, 2015·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Shinji KobuchiToshiyuki Sakaeda
Feb 1, 2005·Drug Metabolism and Pharmacokinetics·Kiyoshi Yamaoka, Yoshinobu Takakura
Nov 28, 2016·European Journal of Drug Metabolism and Pharmacokinetics·Shinji KobuchiToshiyuki Sakaeda

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