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.

Does extra-amniotic infection cause preterm labor? Gas-liquid chromatography studies of amniotic fluid in amnionitis, preterm labor, and normal controls.

Gas-liquid chromatography (GLC) was used to identify short-chain organic acid byproducts of bacterial metabolism in amniotic fluid from seven normal control patients, six women with overt amnionitis, and six preterm labor patients. Microbiologic culture for aerobic and anaerobic bacteria was also carried out. Positive GLC findings were generally associated with positive cultures, except in five of the preterm labor patients whose GLCs were positive despite negative cultures. The origin of the short-chain organic acids found in these women is unclear; extra-amniotic bacterial growth may explain this finding.