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  • Title: Pharmacokinetics of theophylline and 3-methylxanthine in guinea pigs. I. Single dose administration.
    Author: Madsen SM, Ribel U.
    Journal: Acta Pharmacol Toxicol (Copenh); 1981 Jan; 48(1):1-7. PubMed ID: 7223434.
    Abstract:
    Aminophylline in the doses 6.31 . 10(-5) mol kg-1 and 2.37 . 10(-4) mol kg-1 (corresponding to 13.8 and 52.0 mg kg-1 respectively) and 3-methylxanthine 2.37 . 10(-4) mol kg-1 (39.4 mg kg-1) was administered to guinea pigs by intravenous bolus injection, n = 7, 10, and 6, respectively. The shape of semilogarithmic plots of all measured plasma theophylline concentrations versus time was compatible with the use of an open 2-compartment pharmacokinetic model assuming first-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.-1, V1 = 392 ml kg-a; high dose: beta = 0.00198 min.-1, V1 = 528 ml kg-1; P less than 0.05). Following the administration of 3-methylxanthine, the observed plasma concentration time course of this pharmacologically active theophylline metabolite could be adequately described be means of the 2-compartment open model. The administered 3-methylxanthine was eliminated unchanged with a first-order rate constant ten times larger than the total elimination rate constant of theophylline itself, the latter being observed after the administration of the equimolar dose of aminophylline (kel 3MX = 0.029 min.-1, kel theophylline = 0.00293 min.-1). Clearance was calculated to 14.4 ml kg-1 min.-1 for 3-methylxanthine and 1.50 ml kg-1 min.-1 for theophylline. When aminophylline 2.37 . 10(-4) mol kg-1 had been administered, 3-methylxanthine was renally eliminated at a constant rate for the first hours after the injection, but it did not only constitute a few per cent of the theophylline-derived urine products.
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