Subject(s)
Calcium Channel Blockers/urine , Methadone/urine , Narcotics/urine , Substance Abuse Detection/methods , Verapamil/urine , Chromatography, High Pressure Liquid , Cross Reactions , False Positive Reactions , Gas Chromatography-Mass Spectrometry , Humans , Immunoenzyme Techniques , Reagent Kits, DiagnosticABSTRACT
Phenelzine is a drug commonly used in the treatment of depression. Fatalities due to phenelzine have been infrequently reported in the medical literature. The authors report two cases in which phenelzine levels in blood at autopsy were 10-50 times greater than therapeutic levels. Although in both cases other drugs were present in elevated levels, the concentrations of phenelzine were so greatly elevated as to be considered as an independent cause of death.
Subject(s)
Antidepressive Agents/poisoning , Phenelzine/poisoning , Adult , Antidepressive Agents/analysis , Drug Overdose , Fatal Outcome , Female , Humans , Liver/drug effects , Phenelzine/analysisABSTRACT
An organic compound that inhibits drug binding in uremia has been isolated from the sera of chronic renal failure patients, and its chemical structure has been determined. Addition of the compound to normal human sera in vitro resulted in drug binding defects similar to those seen in uremia. The purification of this substance was accomplished by n-butyl chloride extraction of acidified (pH 3.0) uremic sera followed by column chromatography, thin-layer chromatography, and paper electrophoresis. From analytical studies including ultraviolet and fluorescence spectroscopy, gas chromatography, chemical ionization and electron impact mass spectrometry, and proton nuclear magnetic resonance spectroscopy, the chemical structure of the uremic binding inhibitor was deduced to be 2-hydroxybenzoylglycine. This confirms the hypothesis that the drug binding defect in uremia is due to the accumulation of endogenous metabolic products rather than an intrinsic structural defect in albumin.
Subject(s)
Hippurates/blood , Pharmaceutical Preparations/metabolism , Uremia/blood , Chemical Phenomena , Chemistry , Hippurates/isolation & purification , Hippurates/pharmacology , Humans , Magnetic Resonance Spectroscopy , Mass Spectrometry , Protein Binding/drug effects , SpectrophotometryABSTRACT
The ionization constants in water for six 3-substituted azuloic acids were determined spectrophotometrically. Conversion of these physical constants to their pKa values allowed a set of Hammett-type sigma values for the substituents on these acids to be calculated. Determination of partition coefficients for nine 1-substituted azulenes allowed Hansch-type pi values to be determined, using azulene as the model compound.
