Fever-induced changes in theophylline pharmacokinetics in rats.

Our aim was to document possible alterations of theophylline pharmacokinetics in rats during fever. Two groups (group A = normothermic controls, group B = fever-induced animals) of Wistar AF IOPS male rats were injected at 19 30 h either with 2 g/kg of brewer's yeast subcutaneously (20% w/v) or with the equivalent volume of saline. Twelve hours later at 07:30 h the two groups received a single 12 mg/kg/IP dose of theophylline. Blood samples were obtained by retro-orbital sinus puncture 0, 0.25, 0.5, 1, 2, 4, 8, 12, 16 and 24 hours after administration. A third group of 10 male IOPS rats (group C) were used under the same experimental conditions in order to determine the influence of brewer's yeast-induced fever on biological parameters. Cmax, Tmax, Cmax/Tmax, T 1/2, Cl, Vd and AUC were determined according to a one-compartment open model. Our results confirm the fever-induced decrease in total plasma proteins and albumin but do not demonstrate any significant change in theophylline pharmacokinetic parameters.