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Effect of age and Billroth gastrectomy on absorption of desmethyldiazepam from clorazepate
Author(s) -
Ochs Hermann R.,
Greenblatt David J.,
Allen Marcia Divoll,
Harmatz Jerold S.,
Shader Richard I.,
Bodem Gunther
Publication year - 1979
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1979264449
Subject(s) - gastrectomy , medicine , gastroenterology , gastric acid , endocrinology , stomach , cancer
The effect of age and Billroth gastrectomy on absorption of desmethyldiazepam (DMDZ) from a single 20‐mg oral dose of its precursor, clorazepate (CZP) dipotassium, was assessed in 24 males. Six were healthy young controls (mean age, 24), 8 were elderly controls (mean age, 66.5 yr) with no gastrointestinal disease, and 10 were patients (mean age, 56) who had undergone Billroth gastrectomy at least 2 yr before. Absent or impaired gastric acid secretion was documented in 6 of the 10 postgastrectomy patients. Weight‐normalized area under the 48‐hr serum DMDZ concentration curve (WtN‐AUC‐48) among elderly controls (mean, 324 units) and gastrectomy patients (401 units) were similar and significantly less than those in young controls (603 units). Peak serum DMDZ concentrations in elderly controls and gastrectomy patients (185 and 216 ng/ml, respectively) were also lower and reached later after the dose (2.2 and 2.3 hr) than in young controls (371 ng/ml; 1.1 hr). Age per se rather than gastrectomy or acid secretion status explained by far most of the overall variability in WtN‐AUC‐48 and peak DMDZ concentration. Thus normal gastric acidity is not essential for absorption of CZP‐derived DMDZ. The appearance of DMDZ in the systemic circulation is reduced in elderly males, irrespective of surgery or gastric acid secretion. This could be explained by age‐related reduction in conversion of CZP to DMDZ or by more extensive distribution of DMDZ in the elderly.