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Cell membrane modifications in rabbit isolated hepatocytes following a chronic amitryptiline treatment

1973; Elsevier BV; Volume: 22; Issue: 7 Linguagem: Inglês

10.1016/0006-2952(73)90365-1

1873-2968

Gian Luigi Corona, Giuseppe Santagostino, Roberto Maffei Facino, Demetro Pirillo,

Pharmacogenetics and Drug Metabolism

The influence of a chronic amitryptiline pretreatment on the transport of the same drug through the cell membrane has been studied in rabbit isolated hepatocytes, comparing the amount of amitryptiline metabolized by intact hepatocytes with that by disrupted ones. The results show that the amitryptiline metabolism in intact hepatocytes from chronically pretreated rabbits is significantly lower than that in the disrupted ones at all incubation times. By contrast this difference is not present between intact and disrupted hepatocytes from untreated rabbits. These findings support evidence for the hypothesis that the amitryptiline pretreatment affects the permeability of the hepatocyte membrane, thus preventing the penetration of the drug itself into the cells and consequently decreasing its metabolism.