Madsen S M, Ribel U
Acta Pharmacol Toxicol (Copenh). 1981 Jan;48(1):8-12. doi: 10.1111/j.1600-0773.1981.tb01580.x.
Following intravenous bolus injection of theophylline 2.37 . 10(-) mol kg-1 to guinea pigs (administered as aminophylline 52.0 mg kg-1), the elimination of the dose was more rapid in a group of 8 guinea pigs that had received theophylline 2.02 . 10(-4) mol kg-1 (aminophylline 44.3 mg kg-1 (aminophylline 44.3 mg kg-1) intraperitoneally twice daily for 12 days prior to the experiment than in a group of 10 non-pretreated guinea pigs of the same age. The difference was statistically significant in Student's t-test (P less than 0.02). The mean values in the group of pretreated animals were: kel 0.00457 min.-1, beta 0.00296 min.-1, clearance 2.04 ml kg-1 min.-1, Vd beta 693 ml kg-1. By way of comparison, the values obtained in non-pretreated guinea pigs were: kel 0.00293 min.-1 beta 0.00198 min.-1, clearance 1.50 ml kg-1 min.-1, Vd beta 757 ml kg-1. This result suggests enzyme induction to occur. The pharmacologically active theophylline metabolite 3-methylxanthine did not accumulate in the plasma during the long-term theophylline administration. The general plasma concentration level was 0-1.8 . 10(-8) mol ml-1 (0-3 microgram ml-1). In 5 per cent of the samples were detected concentrations in the range 1.8 . 10(-8) mol ml-1 (3-12 microgram ml-1), but the time of occurrence was sporadic.
给豚鼠静脉注射2.37×10⁻⁴摩尔/千克的氨茶碱（以52.0毫克/千克的氨茶碱形式给药）后，在一组8只豚鼠中，该剂量的消除速度比另一组10只同龄未预处理的豚鼠更快。这组8只豚鼠在实验前12天每天两次腹腔注射2.02×10⁻⁴摩尔/千克的氨茶碱（44.3毫克/千克的氨茶碱）。在学生t检验中，差异具有统计学意义（P小于0.02）。预处理动物组的平均值为：消除速率常数（kel）0.00457分钟⁻¹，β消除速率常数（beta）0.00296分钟⁻¹，清除率2.04毫升/千克·分钟，β相分布容积（Vd beta）693毫升/千克。相比之下，未预处理豚鼠获得的值为：kel 0.00293分钟⁻¹，beta 0.00198分钟⁻¹，清除率1.50毫升/千克·分钟，Vd beta 757毫升/千克。该结果表明发生了酶诱导。在长期给予氨茶碱期间，具有药理活性的氨茶碱代谢物3-甲基黄嘌呤并未在血浆中蓄积。血浆总体浓度水平为0至1.8×10⁻⁸摩尔/毫升（0至3微克/毫升）。在5%的样本中检测到浓度在1.8×10⁻⁸摩尔/毫升（3至12微克/毫升）范围内，但出现时间是零星的。
