Nonlinear Elimination of methyprylon (cas 125-64-4) (Noludar) in an Overdosed Patient: Correlation of Clinical Effects with Plasma Concentration

Add time:09/24/2019    Source:sciencedirect.com

This is a report of the pharmacokinetics of methyprylon (cas 125-64-4) 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 μg/mL and linear at concentrations < 30 μg/mL, with an apparent half-life of 4.4 h. The concentration of 5-methylpyrithyldione reached a maximum of 17 μg/mL ~ 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 μg/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.

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