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目的 :全面了解一次静注 8 氯腺苷后其代谢产物在大鼠体内药代动力学的规律及特点 ,为临床实验提供理论依据。方法 :给大鼠单次静注 4种剂量 8 氯腺苷后 ,应用HPLC方法测定在体液和组织中 8 氯腺苷代谢产物8 氯肌苷和 8 氯嘌呤的含量。结果 :8 氯腺苷在大鼠体内迅速转化为代谢产物 8 氯肌苷和 8 氯嘌呤。代谢产物之一 8 氯嘌呤半衰期 (t1/2 )有随用药剂量的增加而延长的趋势 ,为 10 .15～ 32 .84min。药时曲线下面积 (areaunderthecurve ,AUC)在 8 氯腺苷剂量增加至 15 0mg·kg-1时不成比例地增高 ,呈非线性动力学消除的特点。另一代谢产物 8 氯肌苷的t1/2 约为 10 0min ,在剂量增加至 10 0mg·kg-1时 ,其AUC不成比例地增加 ,呈非线性动力学消除的特点。除脂肪、脑、睾丸组织外 ,8 氯肌苷和 8 氯嘌呤在体内分布广泛 ,其中肝、肾等代谢和排泄器官的含量较高。药物主要以代谢物形式从尿及胆汁中排泄 ,排泄量占总给药量的 39.81%。结论 :静注 8 氯腺苷后 8 氯嘌呤在大鼠血中迅速生成 ,消除也比较迅速 ,8 氯肌苷在大鼠血中出现较晚 ,消除也比较缓慢 ,两种代谢物在用药剂量 2 5～ 10 0mg·kg-1范围内呈线性动力学消除 ,当剂量增加至 10 0～ 15 0mg·kg-1有非线性动力学消除的趋势。两代谢物广泛分布于各组织
OBJECTIVE: To comprehensively understand the regularity and characteristics of the pharmacokinetics of its metabolites in rats after intravenous injection of 8-chloro-adenosine, and to provide a theoretical basis for clinical trials. Methods: After a single intravenous injection of 4 doses of 8-chloro-adenosine in rats, the content of 8-chloro-adenosine metabolites 8-oxotoside and 8-chloropurine in body fluids and tissues were determined by HPLC. Results: 8-chloro-adenosine was rapidly transformed into metabolite 8-chloro-inosine and 8-chloropurine in rats. The half-life of 8 chloropurine (t1 / 2), one of the metabolites, tended to increase with the dose of the drug, which was 10.15 to 32.84 minutes. The area under the curve (areaunderthecurve, AUC) increased proportionally when the dose of 8-chloro-adenosine increased to 15 0 mg · kg-1, showing a nonlinear kinetic elimination. The other metabolite 8-chloro-inosine had a t1 / 2 of about 10 0 min. When the dose was increased to 10 0 mg · kg-1, the AUC was increased disproportionately with a nonlinear kinetic elimination. In addition to fat, brain, testicular tissue, 8-chloro-inosine and 8-chloropurine are widely distributed in the body, including liver, kidney and other metabolites and excretion of organs is higher. The drug was mainly excreted in the form of metabolites from urine and bile, accounting for 39.81% of the total dose. CONCLUSION: After intravenous injection of 8-chloro-adenosine, 8-chloropurine is rapidly formed in the blood of rats, and the elimination is relatively rapid. 8-chloro-inosine appeared later in the blood of rats and was also eliminated more slowly. The linear kinetics were eliminated in the range of 25 ~ 100 mg · kg-1. When the dose was increased to 10 0 ~ 150 mg · kg-1, the nonlinear kinetics was eliminated. Two metabolites are widely distributed in various tissues