Pharmacokinetic disposition of an immediate-release aminophylline and a sustained-release theophylline formulation in the horse.
The pharmacokinetic disposition of theophylline was determined by high-performance liquid chromatographic analysis of plasma samples from six healthy, adult horses following the administration of intravenous aminophylline (dosed at 9.94 mg/kg as theophylline), immediate-release aminophylline tablets (dosed at 9.94 mg/kg as theophylline), and sustained-release theophylline tablets (dosed at 20 mg/kg). The elimination rate constant (lambda z), apparent volume of distribution (Vz), and clearance (Cl) determined by compartmental analysis of the intravenous data were 0.07 +/- 0.01 h-1, 0.80 +/- 0.06 l/kg, and 0.06 +/- 0.01 l/kg/h (mean +/- SD), respectively. Mean residence time determined by statistical moment theory of the oral data was different (P less than 0.05) for the immediate-release aminophylline (13.8 +/- 2.8 h) and sustained-release theophylline (18.2 +/- 2.3 h) formulation. Immediate-release aminophylline tablets quickly achieved peak theophylline plasma concentration of 11.51 +/- 1.4 micrograms/ml at 1.6 +/- 0.6 h while the sustained-release theophylline tablets were more slowly absorbed and achieved peak theophylline concentrations of 17.20 +/- 1.3 micrograms/ml at 7.3 +/- 1.0 h. Absolute bioavailability was 87% for the immediate-release and 97% for the sustained-release formulation. Using the principle of superposition, a loading dose of 20 mg/kg of the sustained-release formulation followed by maintenance doses of 15 mg/kg every 24 h was predicted to achieve trough-peak theophylline plasma concentrations between 6 and 17 micrograms/ml.
Goetz
T E
TE
Department of Veterinary Clinical Medicine, University of Illinois, Urbana 61801.
Munsiff
I J
IJ
McKiernan
B C
BC
D000628:Aminophylline / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D006207:Half-Life; D006736:Horses / Q000378:metabolism*; D008954:Models, Biological; D011897:Random Allocation; D012984:Software; D013607:Tablets; D013806:Theophylline / Q000008:administration & dosage / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D013607:Tablets; D000628:Aminophylline; D013806:Theophylline