Effect of an experimental malaria infection on the metabolism of phenacetin in the rat isolated perfused liver.
1. The effect of infection with the rodent malaria parasite Plasmodium berghei on the metabolism of phenacetin has been investigated in a rat isolated perfused liver preparation. 2. A bolus dose of phenacetin (10 mg) was introduced into the perfusate reservoir of both control (n = 4) and malaria-infected (n = 4) liver preparations, and samples of bile and perfusate were collected (0-4 h) for hplc analysis of phenacetin, paracetamol and its phase II metabolites. 3. Whereas malaria had no effect on the hepatic clearance of phenacetin (control: 0.64 +/- 0.15 versus malaria: 0.66 +/- 0.14 ml min-1), there was a significant reduction in the hepatic clearance of generated paracetamol (control: 1.22 +/- 0.15 versus malaria: 0.41 +/- 0.08 ml min-1) and the total recovery in bile and perfusate of paracetamol glucuronide (control: 1.18 +/- 0.44 versus malaria: 0.29 +/- 0.20 mg). There was no significant change during malaria infection in the total recovery of either phenacetin (control: 1.30 +/- 0.73 versus malaria: 0.79 +/- 0.36 mg) or paracetamol sulphate (control: 0.81 +/- 0.25 versus malaria: 0.74 +/- 0.16 mg),
Department of Pharmacology and Therapeutics, University of Liverpool, UK.
A P
AP
Glazier
G O
GO
Kokwaro
S
S
Ismail
G
G
Edwards
D000082:Acetaminophen / Q000097:blood; D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000469:parasitology; D008288:Malaria / Q000378:metabolism* / Q000469:parasitology; D008297:Male; D008954:Models, Biological; D010477:Perfusion; D010615:Phenacetin / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D010962:Plasmodium berghei; D051381:Rats; D017208:Rats, Wistar
D000082:Acetaminophen; D010615:Phenacetin