title: Decreased hepatic elimination of pyrimethamine during malaria infection. Studies in the isolated perfused rat liver.
abstract: The elimination of the antimalarial drug pyrimethamine was studied in isolated liver preparations from young rats (80-100 g) infected with merozoites of Plasmodium berghei two weeks earlier. Perfusate half-life of pyrimethamine was increased in livers from M.I. rats (t1/2 beta control group = 56 +/- 11 min vs M.I. group = 101 +/- 12, P less than 0.01), reflecting a decrease in hepatic clearance (3.6 +/- 1.1 ml/min vs 1.9 +/- 0.5 ml/min, P less than 0.01). There was no significant difference in volume of distribution between livers from M.I. and control groups. Intrahepatic concentration of unchanged drug at 3 hr was 4-5-fold greater in livers from infected rats (control group = 4725 +/- 2287 ng/ml vs M.I. group = 22,324 +/- 6824 ng/ml), while liver: perfusate concentration ratios were not significantly different (control group = 30.8 +/- 24.1 vs M.I. group = 35.6 +/- 20.3). We conclude that the hepatic elimination of pyrimethamine is substantially impaired in the malaria-infected rat.
authors.forename: G W
authors.initials: GW
authors.lastname: Mihaly
authors.forename: N M
authors.initials: NM
authors.lastname: Date
authors.forename: J R
authors.initials: JR
authors.lastname: Veenendaal
authors.forename: K T
authors.initials: KT
authors.lastname: Newman
authors.forename: R A
authors.initials: RA
authors.lastname: Smallwood
mesh_terms: D000818:Animals; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008288:Malaria / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D010962:Plasmodium berghei; D011739:Pyrimethamine / Q000378:metabolism*; D051381:Rats
chemical_list: D011739:Pyrimethamine