Metabolism of caffeine and theophylline in rats with malaria and endotoxin-induced fever
1993
Kokwaro, G.O. | Szwandt, I.S.F. | Glazier, A.P. | Ward, S.A. | Edwards, G.
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.
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