title: 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.
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.
authors.affiliation: College of Pharmacy, University of Michigan, Ann Arbor.
authors.forename: J G
authors.initials: JG
authors.lastname: Wagner
authors.forename: P L
authors.initials: PL
authors.lastname: Stetson
authors.forename: J A
authors.initials: JA
authors.lastname: Knol
authors.forename: J C
authors.initials: JC
authors.lastname: Andrews
authors.forename: S
authors.initials: S
authors.lastname: Walker-Andrews
authors.forename: C A
authors.initials: CA
authors.lastname: Knutsen
authors.forename: N
authors.initials: N
authors.lastname: Johnson
authors.forename: D
authors.initials: D
authors.lastname: Prieskorn
authors.forename: P
authors.initials: P
authors.lastname: Terrio
authors.forename: Z
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004285:Dogs; D006801:Humans; D007065:Idoxuridine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008099:Liver / Q000098:blood supply*; D008433:Mathematics; D011817:Rabbits; D013152:Splanchnic Circulation / Q000502:physiology*
chemical_list: D001973:Bromodeoxyuridine; D007065:Idoxuridine