The disposition of doxepin and its active metabolite desmethyldoxepin was investigated in five uremic patients undergoing hemodialysis. The hemodialysis system yielded a mean extraction efficiency of 7.6% for doxepin and 13.9% for desmethyldoxepin. Mean dialysis clearances were 10.8 and 18.1 ml/min for doxepin and desmethyldoxepin, respectively. The drug and metabolite recovery constituted a very small fraction of the body store, i.e., less than 1%. Hemodialysis did not significantly alter the plasma half-life of doxepin, 14.6 +/- 4.3 h, or of desmethyldoxepin, 25.4 +/- 5.5 h. The nondialyzability of both compounds could be attributed to the compounds' protein binding and volume of distribution. The dialysis experiments show that modification of the usual dosage regimen is not necessary during hemodialysis or on dialysis days. The dialysis parameters confirm that hemodialysis is not likely to be of value in the management of acute doxepin poisoning.
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