Plasma concentrations and urinary excretion of the antiarrhythmic quaternary ammonium compound QX-572 in man.

Abstract

A quantitative thin layer chromatographic (TLC) method has been developed for determination of the antiarrhythmic quaternary ammonium compound N,N-bis (phenylcarbamoyl methyl) dimethylammonium chloride (QX-572) in biological materials. Prior to chromatography QX-572 was transferred into chloroform as perchlorate by ion pair extraction. Tritium-labelled QX-572 was used as the internal standard and a TLC scanning spectrophotometer equipped with a linear detector system afforded the required accuracy, specificity and simplicity. The method was used to determine QX-572 in plasma from 11 patients with various cardiac diseases who received QX-572 8 mg/kg body wt. as an intravenous infusion over 30 min. There was a rapid initial decay of the plasma levels from 11.0+/-1.1 mug/ml (mean+/-SE) at the end of infusion to 3.5+/-0.5 mug/ml after 30 min. 240 min after commencement of the infusion the plasma level was 0.7+/-0.1 mug/ml. In these patients 22+/-2% (mean+/-SE) of the total administered dose of QX-572 was excreted unchanged in urine during the 24 hours following infusion of the drug. A second group of 28 patients with acute myocardial infarction also received QX-572 8 mg/kg body wt. Their plasma levels did not differ significantly from those found in the first group of patients. There was a poor correlation between the amount of QX-572 administered and plasma level at the end of the infusion. The study has provided some preliminary data about the pharmacokinetics of QX-572, but before a detailed analysis can be done data from longer periods of observation is required. The present results suggest that in future QX-572 can be administered in a standardized dosage, what would be advantageous in practice.

• Authors: L Rydén, A Berlin, L R Treiber
• Journal: European journal of clinical pharmacology (Eur J Clin Pharmacol) Vol. 8 Issue 3-4 Pg. 277-82 (Apr 04 1975) ISSN: 0031-6970 [Print] Germany
• PMID: 1233225 (Publication Type: Journal Article)

Chemical References

• Anti-Arrhythmia Agents
• Blood Proteins
• Carbamates
• Quaternary Ammonium Compounds

Topics

• Adult
• Aged
• Anti-Arrhythmia Agents (metabolism)
• Blood Proteins (metabolism)
• Carbamates (metabolism)
• Chromatography, Thin Layer
• Female
• Humans
• Infusions, Parenteral
• Male
• Methods
• Middle Aged
• Protein Binding
• Quaternary Ammonium Compounds (metabolism)