Kuze T, Miyazaki H, Taneike T
Department of Veterinary Pharmacology, Faculty of Dairy Science, Rakuno Gakuen University, Hokkaido, Japan.
Nihon Yakurigaku Zasshi. 1988 May;91(5):325-34. doi: 10.1254/fpj.91.325.
The disposition of theophylline (aminophylline) administered either parenterally or orally to anesthetized dogs was studied. Pharmacokinetics of theophylline (8.2 mg/kg, n = 10) following intravenous administration could be analyzed by a two-compartment open model. The half-time (T1/2 beta) of theophylline was 5.63 +/- 0.83 hr, and the volume of distribution (Vd) was 0.73 +/- 0.04 l/kg. The elimination rate constant was 0.37 +/- 0.05 hr-1. Two metabolites of theophylline were isolated from urine and identified as 3-methyl xanthine (3-MX) and 1,3-dimethyl uric acid (1,3-DMU) by HPLC. The dogs excreted about 85% (n = 4) of the dose in urine in 24 hr. The majority (2/3) was excreted as changed theophylline, i.e., 3-MX 40.2 +/- 3.5% and 1,3-DMU 26.2 +/- 4.3%, while unchanged theophylline amounted to 18.2 +/- 2.4%. Absorption of theophylline (8.2 mg/kg, n = 5) administered intramuscularly was good as indicated by its high bioavailability (101.9 +/- 6.5%), but the value of bioavailability was low in oral administration (72.8 +/- 11.8%, n = 5). The percentage of protein binding (about 44%, n = 3-7) did not change by increasing the serum concentration (8.2-24.6 micrograms/ml).
研究了对麻醉犬经肠胃外或口服给予氨茶碱的处置情况。静脉注射氨茶碱（8.2毫克/千克，n = 10）后的药代动力学可用二室开放模型进行分析。氨茶碱的半衰期（T1/2β）为5.63±0.83小时，分布容积（Vd）为0.73±0.04升/千克。消除速率常数为0.37±0.05小时-1。从尿液中分离出氨茶碱的两种代谢产物，通过高效液相色谱法鉴定为3-甲基黄嘌呤（3-MX）和1,3-二甲基尿酸（1,3-DMU）。犬在24小时内将约85%（n = 4）的剂量经尿液排出。大部分（2/3）以变化的氨茶碱形式排出，即3-MX为40.2±3.5%，1,3-DMU为26.2±4.3%，而未变化的氨茶碱占18.2±2.4%。肌肉注射氨茶碱（8.2毫克/千克，n = 5）的吸收良好，其生物利用度较高（101.9±6.5%），但口服给药时生物利用度值较低（72.8±11.8%，n = 5）。通过提高血清浓度（8.2 - 24.6微克/毫升），蛋白结合百分比（约44%，n = 3 - 7）没有变化。
