Metabolism of caffeine and theophylline in rats with malaria and endotoxin-induced fever.
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| Abstract |
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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| Authors | G O Kokwaro, I S Szwandt, A P Glazier, S A Ward, G Edwards |
| Journal | Xenobiotica; the fate of foreign compounds in biological systems (Xenobiotica) Vol. 23 Issue 12 Pg. 1391-7 (Dec 1993) ISSN: 0049-8254 [Print] England |
| PMID | 8135041 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
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