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Tissue Distribution of Diazepam and Its Metabolite Desmethyldiazepam: A Human Autopsy Study
Author(s) -
Friedman H.,
Ochs Hermann R.,
Greenblatt David J.,
Shader Richard I.
Publication year - 1985
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1985.tb02888.x
Subject(s) - adrenal gland , kidney , diazepam , skeletal muscle , endocrinology , medicine , metabolite , adipose tissue , lung , autopsy , chemistry , distribution (mathematics) , pharmacokinetics , pharmacology , mathematical analysis , mathematics
Concentrations of diazepam (DZ) and desmethyldiazepam (DMDZ) were determined quantitatively in the brain, skeletal muscle, heart, liver, lung, fat, adrenal gland, and kidney in 14 autopsied patients who had been treated with DZ or clorazepate (a DMDZ prodrug) during their hospital course. To facilitate interpatient comparisons, all tissue concentrations from the same patient were normalized as ratios to the concentration of DZ or DMDZ found in that patient's skeletal muscle. Tissue uptake ratios were not influenced by gender or chronicity of dosage. Distribution equilibrium was reached in at least two hours. Tissue uptake ratios differed considerably among tissues for DZ and DMDZ. Mean (± SE) DZ uptake ratio was highest for adrenal gland (12.1 ± 5.9), liver (5.9 ± 1.9), heart (4.3 ± 1.0), and kidney (4.0 ± 1.0), with lower values for lung (2.1 ± 0.5), fat (2.2 ± 0.4), and brain (1.9 ± 0.4). Similar patterns were observed for DMDZ, except for significantly lower fat uptake. Extrapolating to an average body composition for a 70 kg man with 16% body fat, the largest fractions of total body stores of DZ would be found in muscle (42%), fat (35%), and liver (12%), with smaller stores in brain (4.3%), lung (3.3%), heart (1.7%), kidney (2.0%), and adrenal gland (0.24%).