title: Hemolysis on intravenous administration of a new calcium antagonist.
abstract: Hemolysis-inducing properties of the new calcium antagonist Ro 40-5967 administered intravenously to 39 healthy male subjects were investigated in a placebo-controlled study. The volunteers were randomized into five parallel groups of 9 subjects each: three groups, receiving infusions of 40 mg Ro 40-5967 in 60, 30, and 15 min, respectively; one group 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 Ro 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 40-5967 in one arm (treatment schedule thereupon discontinued). Serum bilirubin levels also increased in a dose-dependent manner in all groups as compared with placebo. Other parameters of hemolysis remained unchanged; no hemoglobinuria was observed. The intravascular hemolysis observed on infusion limits the therapeutic application of Ro 40-5967 to oral use only.
authors.affiliation: Clin-Pharma Research AG, Center for Clinical Pharmacology, Basel, Switzerland.
authors.forename: C H
authors.initials: CH
authors.lastname: Kleinbloesem
authors.forename: M
authors.initials: M
authors.lastname: Siepmann
authors.forename: W
authors.initials: W
authors.lastname: Kirch
mesh_terms: D000328:Adult; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001663:Bilirubin / Q000097:blood; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006242:Haptoglobins / Q000378:metabolism; D006456:Hemoglobinuria / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020748:Mibefradil; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D001562:Benzimidazoles; D001798:Blood Proteins; D002121:Calcium Channel Blockers; D006242:Haptoglobins; D013764:Tetrahydronaphthalenes; D020748:Mibefradil; D001663:Bilirubin