CONTROLLED-RELEASE DOSAGE FORMS AND GASTROINTESTINAL BLOOD-LOSS - 4 CLINICAL-STUDIES

Four clinical studies were conducted to assess gastrointestinal (GI) b lood loss during use of the OROS(R) dosage form. These were open-label , randomized, parallel studies of 176 healthy volunteers 18-78 years o f age. Blood loss was measured using the Cr-51 red blood cell tagging method and stool guaiac tests. GI blood loss from a drug associated wi th GI irritation, indomethacin [as OROS (sodium indomethacin) or as im mediate-release indomethacin], was greater than that from lactose plac ebo but less than that from aspirin. GI blood loss following ingestion of the OROS dosage forms containing cold/allergy drugs - a combinatio n of pseudoephedrine hydrochloride and brompheniramine maleate, chlorp heniramine maleate, or pseudoephedrine hydrochloride - was statistical ly indistinguishable from that of marketed reference slow-release cold /allergy products or placebos. Blood loss in volunteers 50 years of ag e or older was similar during use of OROS (mannitol) placebo or oral l actose placebo tablets. Baseline GI blood loss in all four studies was age-invariant. In these studies, GI blood loss, when present, was ass ociated with specific drugs, aspirin and indomethacin, and not with a particular OROS dosage form.