Comparative pharmacokinetics of midazolam and loprazolam in healthy subjects after oral administration

• Published in: Biopharmaceutics & drug disposition Vol. 7; no. 1; p. 53
• Main Authors: Jochemsen, R, van Rijn, P A, Hazelzet, T G, van Boxtel, C J, Breimer, D D
• Format: Journal Article
• Language: English
• Published: England 01-01-1986
• Subjects: Administration, Oral; Adult; Anti-Anxiety Agents - administration & dosage; Anti-Anxiety Agents - metabolism; Benzodiazepines - administration & dosage; Benzodiazepines - blood; Benzodiazepines - metabolism; Benzodiazepinones - administration & dosage; Benzodiazepinones - blood; Benzodiazepinones - metabolism; Chromatography, Gas; Female; Half-Life; Humans; Kinetics; Male; Midazolam; Radioligand Assay
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510070108

The pharmacokinetics of oral midazolam (Dormicum, 15 mg) and loprazolam (Dormonoct, 1 mg) were studied in eight healthy young volunteers in a cross-over design. Plasma concentrations of midazolam were measured with a gas chromatographic method and loprazolam concentrations were determined by a radio-receptor technique. Absorption of midazolam proceeded very rapidly (median tmax = 0.4 h) and a rapid onset of sedative action was observed. Loprazolam absorption was relatively slow (median tmax = 3 h) and its absorption profile was often irregular. Most subjects fell asleep before peak concentrations were reached. Median peak concentrations were 94 ng ml-1 and 3.1 ng ml-1 for midazolam and loprozolam, respectively. The median elimination half-life of midazolam was 1.8 h and that of loprazolam 15 h. It is possible that the elimination half-life of loprazolam as determined by radioreceptor assay is determined by active metabolites rather than by loprazolam itself. Midazolam elimination half-life was the same when determined by radioreceptor assay or by GLC. There was no significant correlation between the half-lives of the two drugs.