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.
Department of Pharmacology, College of Medicine, Ohio State University, Columbus 43210.
D A
DA
Contos
K F
KF
Dixon
R M
RM
Guthrie
N
N
Gerber
D C
DC
Mays
D000328:Adult; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D006801:Humans; D010881:Piperidones / Q000097:blood / Q000493:pharmacokinetics* / Q000506:poisoning; D011728:Pyridones / Q000097:blood; D013056:Spectrophotometry, Ultraviolet; D013405:Suicide
D010881:Piperidones; D011728:Pyridones; C040455:5-methylpyrithyldione