GASTRIC-MUCOSAL ADAPTATION TO DICLOFENAC INJURY

Adaptation occurs to the gastric injury produced by nonsteroidal antii nflammatory drugs during continued dosing, The aim of this study was t o identify characteristics of this phenomenon that might help in the s earch for underlying mechanisms. The time frame for onset and offset o f adaptation of diclofenac (damage assessed planimetrically) was exami ned in rats. Adaptation to oral diclofenac took three to five days to develop, and persisted for up to five days after the last dose, It was also demonstrable after subcutaneous dosing or when injury was measur ed by a change in mucosal potential difference. Diclofenac-adapted rat s were protected against injury induced by subsequent exposure to etha nol, indomethacin, aspirin, or piroxicam, indicating that adaptation i s not specific to injury by the adapting agent. This cross-adaptation was dose-dependent and characterized histologically by a reduction in deep damage, In conclusion, gastric adaptation to diclofenac is mediat ed by mechanisms that take several days to develop and be lost. The ro ute of administration appears to be unimportant, but the development o f both adaptation and cross-adaptation is influenced by dosage size.