Theophylline and dyphylline pharmacokinetics in the horse.
The pharmacokinetics of theophylline and dyphylline were determined after IV administration in horses. In a preliminary experiment, the usual human dosage (milligram per kilogram) of each drug was given to 1 horse. Results were used to calculate dosages for a cross-over study, using 6 horses for each drug. Theophylline plasma concentrations decreased triexponentially in 5 of 6 healthy horses after IV infusion of 10 mg of aminophylline/kg of body weight for 16 to 32 minutes. In the 6 horses, total body elimination rate constants were variable, and the half-life of theophylline was 9.7 to 19.3 hours. Clearance was 42.3 to 69.2 ml/hr/kg. The initial distribution phase was rapid (t1/2 approx 3.5 to 4 minutes); a 2nd distribution phase was slower (t1/2 approx 1.5 to 2 hours). Plasma concentrations of theophylline were in the assumed effective range (10 to 20 micrograms/ml) from 15 minutes until 40 minutes after time zero. The mean apparent volume of distribution was 1.02 L/kg. After bolus IV injection of dyphylline (20 mg/kg), pharmacokinetics were best described by a 2-compartment open model in 2 horses and by a 3-compartment open model in 4 horses. In the 6 horses, elimination half-life of dyphylline was 1.9 to 2.9 hours, and clearance was 200 to 320 ml/hr/kg. Plasma concentrations (approx 50 micrograms/ml) were observed at 10 minutes after injection without adverse effects. Concentrations greater than 10 micrograms/ml were observed from time zero to about 1.5 hours after injection. Theophylline induced significant increases in heart rate, but dyphylline did not affect heart rate significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
D000628:Aminophylline / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004400:Dyphylline / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D005260:Female; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006736:Horses; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D013806:Theophylline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood* / Q000494:pharmacology
D004400:Dyphylline; D000628:Aminophylline; D013806:Theophylline