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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Nonlinear elimination of methyprylon (noludar) in an overdosed patient: correlation of clinical effects with plasma concentration.

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.[1]


  1. Nonlinear elimination of methyprylon (noludar) in an overdosed patient: correlation of clinical effects with plasma concentration. Contos, D.A., Dixon, K.F., Guthrie, R.M., Gerber, N., Mays, D.C. Journal of pharmaceutical sciences. (1991) [Pubmed]
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