Metabolism of caffeine and theophylline in rats with malaria and endotoxin-induced fever.
1. The effects of malaria infection due to Plasmodium berghei and Escherichia coli endotoxin-induced fever on the metabolism of orally-administered caffeine (CA: 10 mg/kg) to its primary metabolites (theobromine (TB), paraxanthine (PX) and theophylline (TH)) were studied in 5-week-old male Wistar rats (n = 5 for each treatment). In separate experiments, the effects of malaria and endotoxin-induced fever on the clearance of i.v.-administered theophylline (TH; 15 mg/kg) were studied in another group of rats. 2. The ratios of CA to the three primary metabolites (TB/CA, PX/CA, PH/CA) determined in a single plasma sample obtained 3 h after CA administration were significantly reduced (p < 0.05) both by malaria and fever compared with control (saline) treatment. The clearance of TH determined from the concentration of TH in a single plasma sample obtained 6 h after TH administration was significantly reduced (p < 0.05) by fever but not malaria (4.0 +/- 0.7 ml/min/kg in controls; 4.2 +/- 0.5 in malaria; 2.4 +/- 0.4 in fever). 3. These results suggest that malaria and fever have different effects on CA and TH metabolism in vivo, probably as a result of different effects on the hepatic isozymes involved.
Kokwaro
G O
GO
Department of Pharmacology and Therapeutics, University of Liverpool, UK.
Szwandt
I S
IS
Glazier
A P
AP
Ward
S A
SA
Edwards
G
G
D000284:Administration, Oral; D000818:Animals; D002110:Caffeine / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D004731:Endotoxins / Q000633:toxicity; D005334:Fever / Q000139:chemically induced / Q000378:metabolism*; D007275:Injections, Intravenous; D008288:Malaria / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D010962:Plasmodium berghei; D051381:Rats; D017208:Rats, Wistar; D013805:Theobromine / Q000378:metabolism; D013806:Theophylline / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics
D004731:Endotoxins; D002110:Caffeine; C044101:endotoxin, Escherichia coli; D013806:Theophylline; D013805:Theobromine; C021183:1,7-dimethylxanthine