Pharmacokinetics of Theophylline and 3‐Methylxanthine in Guinea Pigs. I. Single Dose Administration

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Abstract
Aminophylline in the doses 6.31 .cntdot. 10-5 mol/kg and 2.37 .cntdot. 10-4 mol/kg (corresponding to 13.8 and 52.0 mg/kg, respectively) and 3-methylxanthine [3-MX] 2.37 .cntdot. 10-4 mol/kg (39.4 mg/kg) was administered to guinea pigs by i.v. bolus injection, n = 7, 10 and 6, respectively. The shape of semilogarithmic plots of all measured plasma theophylline concentrations vs. time was compatible with the use of an open 2-compartment pharmacokinetic model assuming 1st-order distribution and elimination processes, but in the comparison of the mean values of the pharmacokinetic parameters obtained after the administration of the low and the high theophylline dose, statistical analysis by Student''s t-test showed .beta. and V1 to be significantly altered (low dose: .beta. = 0.00338/min., V1 = 392 ml/kg; high dose: .beta. = 0.00198/min, V1 = 528 ml/kg; P < 0.05). Following the administration of 3-MX the observed plasma concentration time course of this pharmacologically active theophylline metabolite could be adequately described by means of the 2-compartment open model. The administered 3-MX was eliminated unchanged with a 1st-order rate constant 10 times larger than the total elimination rate constant [kel] of theophylline itself, the latter being observed after the administration of the equimolar dose of aminophylline (kel 3MX = 0.029/min, kel theophylline = 0.00293/min). Clearance was calculated to 14.4 ml/kg min for 3-MX and 1.50 ml/kg per min for theophylline. When aminophylline 2.37 .cntdot. 10-4 mol/kg was administered, 3-MX was renally eliminated at a constant rate for the 1st hours after the injection, but it did only constitute a few percent of the theophylline-derived urine products.