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.

Difficult nasotracheal intubation: a previously unreported anatomical cause.

Anatomic and congenital abnormalities of the nasal pharynx may make nasotracheal intubation difficult. We present a case of a patient who was comatose from a drug overdose and who required endotracheal intubation. Blind nasotracheal intubation was attempted and was initially unsuccessful due to the presence of a congenital pharyngeal bursa. After the cause of the obstruction was recognized, guided nasotracheal intubation was accomplished without complications. The patient made an uneventful recovery.

Interpretation of blood glutethimide, meprobamate, and methyprylon concentrations in nonfatal and fatal intoxications involving a single drug.

We evaluated blood concentrations of three nonbarbiturate sedative-hypnotics in 19 nonfatal (NF) and five fatal (F) intoxications which were "pure" (i.e. which involved only one drug each): glutethimide, 4 (NF), 3 (F); meprobamate, 9 (NF), 1 (F); and methyprylon, 6 (NF), 1 (F). For each of the 24 cases, both a comprehensive toxicology panel (including blood and urine) and the clinical history established that only a single drug had been ingested. Blood drug concentrations showed statistically significant correlation with the level of consciousness for nonfatal meprobamate intoxication (p less than 0.01) and nonfatal methyprylon intoxication (p less than 0.05). Blood glutethimide concentrations did not show such correlation. Death was associated with a mean blood glutethimide concentration in excess of 4.0 mg/dL, a blood meprobamate concentration of 20.5 mg/dL, and a blood methyprylon concentration of 11.7 mg/dL. Interpretation of blood concentrations of these compounds is discussed, and physical findings and demographic data are presented.

The effect of oral castor oil on the disposition of methyprylon in intoxicated dogs.

Clinical observations indicate that large oral doses of castor oil are effective in reducing the time of coma resulting from acute intoxication with lipophilic drugs. It has been further suggested that the rate of removal of these drugs from the body is increased by castor oil. In order to investigate the effect of castor oil on the disposition of lipophilic drugs, five dogs were given toxic doses of methyprylon by intravenous infusion. Each dog was treated with a large oral dose of castor oil in a cross-over fashion. No significant difference was observed in the sleep times of the dogs treated with castor oil, or in the methyprylon pharmacokinetics compared to controls. It was concluded that castor oil does not affect the disposition of methyprylon.

Peritoneal dialysis for severe methyprylon intoxication.

The appropriate therapy for methyprylon (Noludar) poisoning has remained controversial, owing to a lack of reliable pharmacologic data concerning the most effective way to remove the drug after a large ingestion. We recently employed peritoneal dialysis to treat a 16-year-old girl, who had ingested 6.3 gm of methypyrlon, and were able to recover more than 80% of the unmetabolized drug in the dialysate. Clinical recovery was complete within eight hours. This appears to be a safe and effective method to remove the drug in the child or adult with a serious intoxication.

Hemodialysis in methyprylon overdose. Some pharmacokinetic considerations.

Serial measurements of serum methyprylon concentration were made in the case of a 14-year-old girl who ingested an overdose of the drug. Our data indicate that, in the presence of high plasma levels of the drug, much longer half-lives than the usually reported four hours may be observed. It is postulated that saturation kinetics may be a possible mechanism for this observation. The striking clinical improvement after six hours of hemodialysis demonstrated the efficacy of this mode of treatment in our patient.

The reduction of coma time in lipophilic drug overdose using castor oil.

A clinical trial of castor oil in overdoses of lipophilic drugs gave a strong clinical impression that it was effective in speeding up recovery. Therefore, animal experiments were undertaken to confirm that castor oil acts as a ligand in Ethchlorvynol poisoning and that its use reduces coma time. Serial serum levels of Ethchlorvynol were obtained from dogs given Ethchlorvynol 150 mg/kg alone, and the same dose dissolved in castor oil 15 ml/kg in a crossover fashion. The result was a reduction of peak serum levels and of the half-life of the drug when the castor oil solution was used. In order to mimic the clinical situation more closely, a further crossover study was undertaken using Ethchlorvynol 300 mg/kg alone and the same dose followed by castor oil 15 ml/kg repeated q12h. This showed no delay in reaching peak serum concentration and no reduction of peak levels. However, it did show a 31 per cent reduction in the half-life of the drug. This change is statistically significant, and supports the continued use of castor oil in lipophilic drug overdose.

Microcapsule artificial kidney: treatment of patients with acute drug intoxication.

The microcapsule artificial kidney was used in the treatment of three patients with acute drug intoxication. The apparatus contains 300 g. of microencapsulated activated charcoal with a total membrane area available for diffusion of more than 2m.(2) The membrane thickness is only 500 A. These properties make possible a compact artificial kidney whose efficiency for the removal of uremic metabolites and drugs is much higher than standard hemodialysis apparatus. The microcapsules are made blood-compatible by coating with human albumin. A roller pump was used to propel the blood through the microcapsule artificial kidney at a flow rate of 300 ml./min. for two to three hours. The clearance values for glutethimide, methyprylon and methaqualone were much higher than those achieved by standard hemodialysis. Hemoperfusion quickly lowered the drug level in the blood with resulting clinical improvement.