Comparative pharmacokinetics of midazolam and loprazolam in healthy subjects after oral administration.
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.
Jochemsen
R
R
van Rijn
P A
PA
Hazelzet
T G
TG
van Boxtel
C J
CJ
Breimer
D D
DD
D000284:Administration, Oral; D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000378:metabolism*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D002849:Chromatography, Gas; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D008874:Midazolam; D011869:Radioligand Assay
D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D001569:Benzodiazepines; C020168:triazulenone; D008874:Midazolam