EFFECT OF AGE AND BILLROTH GASTRECTOMY ON ABSORPTION OF DESMETHYLDIAZEPAM FROM CLORAZEPATE

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 (an antianxiety agent), was assessed in 24 males. Six were healthy young controls (mean age, 24 yr), 8 were elderly controls (mean age, 66.5 yr) with no gastrointestinal disease, and 10 were patients (mean age, 56 yr) 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 h serum DMDZ concentration curve (WtN-AUC-48) among elderly controls, (mean, 324 units [U]) and gastrectomy patients (401 U) were similar and significantly < those in young controls (603 U). 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 h) than in young controls (371 ng/ml; 1.1 h). Age rather than gastrectomy or acid secretion status explained most of the overall variability in WtN-AUC-48 and peak DMDZ concentration. 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.