AbstractCimetidine and ranitidine absorption were studied in rats, alone or in combination with concurrent but separate bupropion oral admininstration. Blood samples were collected before and 0·25, 0·5, 0·75, 1·0, 1·5, 2·0, 3·0, 4·5, and 6·0h after dosing. In ranitidinetreated rats, an exta blood sample at 8h was collected. Assays of cimetidine and ranitidine were carried out using a HPLC method. Mean cimetidine plasma concentrations on concurrent bupropion administration at 0·25 and 0·5 h were approximately 2 and 1·5 times compared to the control. Similarly, mean ranitidine plasma concentrations with bupropion combination at 0·25 and 0·5 h were significantly different and approximately 2 and 3 times higher. Time of maximum concentration for cimetidine and ranitidine on combination were reduced to almost half of the control value. However, only the time of maximum concentration for cimetidine showed statistically significant difference. No significant differences were observed between AUCs, maximum concentrations, and half‐lives of cimetidine and ranitidine compared to their respective controls. The results suggest that concurrent bupropion admininstration may affect the rate but not the extent of absorption of cimetidine