Minimal biliary excretion and enterohepatic recirculation of lormetazepam in man as investigated by a new nasobiliary drainage technique.
The pharmacokinetics of lormetazepam (LMA) was studied in five patients with intact and interrupted enterohepatic recirculation (EHR) after an oral dose of 0.03 mg/kg given as solution. The disposition of lormetazepam in plasma was characterized by peak plasma levels of 14-60 ng/ml after 20-40 min. Peak plasma levels of the unchanged drug were higher (p less than 0.05) in case of interrupted EHR as compared to intact EHR. The areas and the plasma levels vs time curves of lormetazepam and its glucuronide were not statistically different and the oral clearance of lormetazepam was similar in both parts of the study (median 3.1 and 3.6 ml/min/kg). In case of interrupted EHR, 23-58% of dose was excreted as lormetazepam and its glucuronide with the urine during 24 h, in case of intact EHR, the urinary dose fraction was 9-35% (p less than 0.05). The 24 h postdose-bile fraction contained only 0.3-2.8% of the oral lormetazepam dose in form of the drug and its glucuronide. In conclusion, only negligible amounts of lormetazepam are excreted in bile. The demethylated metabolite lorazepam was not detectable in the biological samples investigated.
Hellstern
A
A
Department of Pharmacokinetics, Schering AG, Berlin/Berkamen, FRG.
Hildebrand
M
M
Hümpel
M
M
Hellenbrecht
D
D
Saller
R
R
Madetzki
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics*; D001569:Benzodiazepines; D001646:Bile / Q000378:metabolism*; D001711:Biotransformation; D002779:Cholestasis / Q000378:metabolism; D004764:Enterohepatic Circulation; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D006801:Humans; D008140:Lorazepam / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged
D014151:Anti-Anxiety Agents; D005965:Glucuronates; D001569:Benzodiazepines; C023842:lormetazepam; D008140:Lorazepam