Madsen S M, Ribel U
Acta Pharmacol Toxicol (Copenh). 1981 Jan;48(1):1-7. doi: 10.1111/j.1600-0773.1981.tb01579.x.
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.
分别以6.31×10⁻⁵mol/kg和2.37×10⁻⁴mol/kg（分别相当于13.8mg/kg和52.0mg/kg）的剂量以及2.37×10⁻⁴mol/kg（39.4mg/kg）的3-甲基黄嘌呤通过静脉推注给予豚鼠，每组动物数量分别为7只、10只和6只。所有测得的血浆茶碱浓度对时间的半对数图形状符合采用开放二室药代动力学模型，该模型假设存在一级分布和消除过程，但在比较低剂量和高剂量茶碱给药后获得的药代动力学参数平均值时，经学生t检验的统计分析表明β和V₁有显著变化（低剂量：β = 0.00338min⁻¹，V₁ = 392ml/kg；高剂量：β = 0.00198min⁻¹，V₁ = 528ml/kg；P＜0.05）。给予3-甲基黄嘌呤后，该具有药理活性的茶碱代谢产物的血浆浓度-时间过程可用二室开放模型充分描述。给予的3-甲基黄嘌呤以未变化的形式消除，其一级速率常数比茶碱本身的总消除速率常数大10倍，后者是在给予等摩尔剂量的氨茶碱后观察到的（3-甲基黄嘌呤的kel = 0.029min⁻¹，茶碱的kel = 0.00293min⁻¹）。计算得出3-甲基黄嘌呤的清除率为14.4ml/kg·min，茶碱的清除率为1.50ml/kg·min。当给予2.37×10⁻⁴mol/kg的氨茶碱后，注射后的最初几个小时内3-甲基黄嘌呤以恒定速率经肾消除，但它仅占源自茶碱的尿产物的百分之几。
