HEMOLYSIS ON INTRAVENOUS ADMINISTRATION OF A NEW CALCIUM-ANTAGONIST

Hemolysis-inducing properties of the new calcium antagonist Ro 40-5967 administered intravenously to 39 healthy male subjects were investiga ted in a placebo-controlled study. The volunteers were randomized into five parallel groups of 9 subjects each: three groups receiving infus ions of 40 mg Po 40-5967 in 60, 30, and 15 min, respectively; one grou p receiving 80 mg Ro 40-5967 in 30 min as two simultaneous doses of 40 mg in the cubital veins of both arms; and one group receiving 80 mg R o 40-5967 in 30 min in one arm. Within each group, 3 subjects received placebo under randomized double-blind conditions. Plasma haptoglobin decreased by 67% after 3.5 h in 2 subjects who received 80 mg Ro 40-59 67 in one arm (treatment schedule thereupon discontinued). Serum bilir ubin levels also increased in a dose-dependent manner in all groups as compared with placebo. Other parameters of hemolysis remained unchang ed; no hemoglobinuria was observed. The intravascular hemolysis observ ed on infusion limits the therapeutic application of Ro 40-5967 to ora l use only.