Premium
Clinical Pharmacokinetics of Lorazepam. IV. Long‐Term Oral Administration
Author(s) -
GREENBLATT DAVID J.,
KNOWLES JOHN A.,
COMER WALTER H.,
SHADER RICHARD I.,
HARMATZ JEROLD S.,
RUELIUS HANS W.
Publication year - 1977
Publication title -
the journal of clinical pharmacology
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1977.tb05642.x
Subject(s) - lorazepam , pharmacokinetics , discontinuation , medicine , metabolite , anesthesia , oral administration , glucuronide , pharmacology
Fifteen healthy male volunteers received long-term daily treatment with oral lorazepam at doses as high as 10 mg per day for a period of 26 weeks. Steady-state plasma concentrations of lorazepam and its glucuronide metabolite were measured in all subjects at least every two weeks. At daily doses of 6 mg per day, the mean steady-state lorazepam level was 88 ng/ml and that of lorazepam glucuronide was 170 ng/ml. Mean levels among seven subjects who received 10 mg per day were 164 and 266 ng/ml, respectively. Lorazepam concentrations fluctuated from week to week despite constant dosage, but there was no evidence of systematic variation. Mean steady-state lorazepam levels were highly correlated with daily dose in mg/kg, but were not related to age. Lorazepam was not detected in any plasma samples drawn one week after discontinuation of treatment.