Effect of Abdominal Radiation Therapy on Drug Absorption in Humans

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Abstract
The absorption of oral digoxin and of demethyldiazepam, from its precursor clorazepate, was studied in 7 patients who received abdominal and/or pelvic radiation therapy for neoplastic disease. All patients were in remission and had normal renal function and no evidence of malabsorption. Single 0.5 mg doses of digoxin tablets and 15 mg doses of clorazepate were administered in the fasting state. Concentrations of digoxin (by radioimmunoassay) and demethyldiazepam (by gas chromatography) were determined in multiple plasma samples and all urine collected during 24 h after dosage. The mean (.+-. SE) weight-normalized area under the 24 h plasma digoxin concentration curve (WtN-AUC-24) in the patients (722 .+-. 40 ng/ml h kg) was similar to that in 5 normal controls (713 .+-. 57 ng/ml h kg), but 24 h urinary excretion of digoxin in patients (54.5 .+-. 4.4 .mu.g) was significantly less (P < 0.025) than in controls (83.4 .+-. 11.4 .mu.g). Neither age, sex nor renal function explained the difference. In the clorazepate study, WtN-AUC-24 for demethyldiazepam in the patients (187 .+-. 19 .mu.g/ml h kg) was significantly less (P < 0.01) than in 15 normal control subjects (230 .+-. 5 .mu.g/ml h kg). Age and sex did not explain the difference. Thus, radiation therapy, or the underlying disease, was associated with malabsorption of these 2 drugs, possibly because of damage to gastric acid-secreting cells.

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