Contos D A, Dixon K F, Guthrie R M, Gerber N, Mays D C
Department of Pharmacology, College of Medicine, Ohio State University, Columbus 43210.
J Pharm Sci. 1991 Aug;80(8):768-71. doi: 10.1002/jps.2600800813.
This is a report of the pharmacokinetics of methyprylon and its major plasma metabolite, 5-methylpyrithyldione, in an overdosed patient using a reversed-phase HPLC assay. The decline in the concentration of plasma methyprylon was nonlinear between 66 and 30 micrograms/mL and linear at concentrations less than 30 micrograms/mL, with an apparent half-life of 4.4 h. The concentration of 5-methylpyrithyldione reached a maximum of 17 micrograms/mL approximately 13 h after admission and declined with a half-life of 8 h. Treatment of the patient was conservative, consisting of gastric lavage and supportive therapy. The patient regained consciousness when the methyprylon concentration fell below 43 micrograms/mL, and recovered from the overdose within 24 h. These results indicate that the pharmacokinetics of methyprylon are nonlinear (concentration dependent) in this overdosed patient; explanations include saturation of one or more of the metabolic pathways and/or product inhibition. The 4-h half-life of methyprylon, generally accepted for a therapeutic dose of 300 mg, is not appropriate in intoxicated patients and would greatly underestimate the time required to reach a safe therapeutic concentration of the drug.
这是一篇关于使用反相高效液相色谱法测定一名过量服药患者中甲丙氨酯及其主要血浆代谢物5-甲基吡啶二酮药代动力学的报告。血浆中甲丙氨酯浓度在66至30微克/毫升之间呈非线性下降，而在浓度低于30微克/毫升时呈线性下降，表观半衰期为4.4小时。5-甲基吡啶二酮浓度在入院后约13小时达到最高值17微克/毫升，并以8小时的半衰期下降。对该患者的治疗是保守的，包括洗胃和支持治疗。当甲丙氨酯浓度降至43微克/毫升以下时患者恢复意识，并在24小时内从过量服药中康复。这些结果表明，在这名过量服药患者中甲丙氨酯的药代动力学呈非线性（浓度依赖性）；原因包括一种或多种代谢途径的饱和及/或产物抑制。甲丙氨酯通常接受的治疗剂量为300毫克时的4小时半衰期，在中毒患者中并不适用，会极大低估达到药物安全治疗浓度所需的时间。
