Chlormezanone plasma and blood levels in patients after single and repeated oral doses and after suicidal drug overdose.
Chlormezanone plasma concentrations were determined in 5 volunteers (group 1) after a single oral dose of 200 mg of chlormezanone with high performance liquid chromatography. A plasma elimination half-life of 23 +/- 2.3 h was calculated. The mean peak chlormezanone plasma level was 1.86 +/- 0.2 micrograms/ml, 1 h after ingestion. Additionally, chlormezanone plasma levels were determined after repeated oral doses of chlormezanone recommended for treatment of muscular spasms due to degenerative skeletal disease. After 5 days of repeated daily doses of 3 x 200 mg (group 2; 12 patients) or 3 x 400 mg (group 3; 10 patients) of chlormezanone, mean predose chlormezanone plasma levels were 12.0 +/- 2.0 micrograms/ml (group 2) and 22.7 +/- 4.0 micrograms/ml (group 3), respectively. Comparable plasma concentrations were determined after 10 days of repeated doses of 3 x 200 mg or 3 x 400 mg of chlormezanone in 3 patients from each of these 2 groups. In 7 patients of group 3, chlormezanone had to be discontinued on the 5th day due to increasing muscular weakness, ataxia and exercise-inducible tachycardia. After a loading dose of 800 mg and repeated doses of 3 x 200 mg chlormezanone to 5 patients (group 4), plasma levels of 6.5 +/- 2.1 micrograms/ml, 8.9 +/- 2.2 micrograms/ml, 12.7 +/- 2.0 micrograms/ml, and 10.4 +/- 2.4 micrograms/ml were determined after 2, 8, 16, and 36 h, respectively. Trace amounts of a degradation product of the acid-labile chlormezanone could be detected in plasma besides the unchanged drug after administration of repeated oral doses.(ABSTRACT TRUNCATED AT 250 WORDS)
Köppel
C
C
Reanimationszentrum, Klinikum Rudolf Virchow, Freie Universität Berlin, Germany.
Kristinsson
J
J
Wagemann
A
A
Tenczer
J
J
Martens
F
F
D000082:Acetaminophen / Q000506:poisoning; D000284:Administration, Oral; D000328:Adult; D002720:Chlormezanone / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000506:poisoning; D002851:Chromatography, High Pressure Liquid; D003975:Diazepam / Q000506:poisoning; D004338:Drug Combinations; D062787:Drug Overdose; D005260:Female; D006801:Humans; D007928:Lethal Dose 50; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000378:metabolism; D013405:Suicide; D014018:Tissue Distribution
D004338:Drug Combinations; D000082:Acetaminophen; D002720:Chlormezanone; D003975:Diazepam