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.
Bruguerolle
B
B
Laboratoire de Pharmacologie Médicale et Clinique, Faculté de Médecine de Marseille, France.
Dubus
J C
JC
D000818:Animals; D001663:Bilirubin / Q000097:blood; D001798:Blood Proteins / Q000032:analysis; D001831:Body Temperature / Q000502:physiology; D003404:Creatinine / Q000097:blood; D005334:Fever / Q000097:blood / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000032:analysis; D013806:Theophylline / Q000097:blood / Q000493:pharmacokinetics*; D014508:Urea / Q000097:blood; D005723:gamma-Glutamyltransferase / Q000097:blood
D001798:Blood Proteins; D012709:Serum Albumin; D014508:Urea; D003404:Creatinine; D013806:Theophylline; D005723:gamma-Glutamyltransferase; D001663:Bilirubin