Steady-state arterial and hepatic venous plasma concentrations of 5-bromo-2'-deoxyuridine and 5-iodo-2'-deoxyuridine in animals--drugs which are subject to both splanchnic and extra-splanchnic elimination

Sel Cancer Ther. 1989 Winter;5(4):193-203. doi: 10.1089/sct.1989.5.193.

Abstract

We have previously shown that 5-fluorouracil (FUra) in humans obeys Michaelis-Menten elimination kinetics. In this article we show that the related bromine and iodine-containing analogs in animals obey similar kinetics. Steady-state arterial (CssA) and hepatic venous plasma (CssV) concentrations of 5-bromo-2'-deoxyuridine (BrdUrd) are reported for 7 rabbits given 5 different infusion rates of BrdUrd and 5 dogs given 4 or 5 different infusion rates of BrdUrd. Steady-state arterial and hepatic venous plasma concentrations of 5-iodo-2'-deoxyuridine (IdUrd) are reported for 5 rabbits and 2 dogs given 5 different infusion rates of IdUrd. Each set of data could be fitted by a nonlinear least squares method to the equation: (equation; see text) where Vm/Q is the maximum difference, (CssA) - (CssV), and Km is the Michaelis constant. The estimated parameter Vm/Q and Km are compared for the two drugs and different species and also with the same parameters derived in the same manner from previously published data on fluorouracil in 8 cancer patients. The infusion rate needed to saturate the splanchnic elimination system (Rs in mumol/kg/min) was also estimated. For BrdUrd the mean value of Rs in the rabbit, namely 1.23, and in the dog, namely 1.25 mumol/kg/min are essentially the same.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bromodeoxyuridine / administration & dosage
  • Bromodeoxyuridine / blood
  • Bromodeoxyuridine / pharmacokinetics*
  • Dogs
  • Humans
  • Idoxuridine / administration & dosage
  • Idoxuridine / blood
  • Idoxuridine / pharmacokinetics*
  • Liver / blood supply*
  • Mathematics
  • Rabbits
  • Splanchnic Circulation / physiology*

Substances

  • Bromodeoxyuridine
  • Idoxuridine