title: Clinical evaluation on combined administration of oral prostacyclin analogue beraprost and phosphodiesterase inhibitor cilostazol.
abstract: Among various oral antiplatelets, a combination of a novel prostacyclin analogue beraprost (BPT) and a potent phosphodiesterase inhibitor cilostazol (CLZ) may result in untoward clinical effects due to possible synergistic elevation of intracellular cAMP (cyclic adenosine 3',5'-monophosphate). Thereby, a clinical study of the combined administration of the two agents was attempted. Twelve healthy volunteers were assigned to take BPT/CLZ in the following schedule; BPT: 40 micrograms at day 1 and 120 micrograms t.i.d. from day 7 to 14, CLZ: 200 mg t.i.d. from day 3 to 14. At various time intervals, physical examination and blood collection for ex vivo platelet aggregation and determination of intraplatelet cAMP were performed. Throughout the observation period, no significant alteration in vital signs was observed. Seven out of 12 subjects experienced headache of a short duration accompanying facial flush in one and nausea in one, especially after ingestion of CLZ. All of these symptoms, probably caused by the vasodilating effect of the two agents, were of mild degree and no special treatment was required. Intraplatelet cAMP content was gradually but significantly increased to 9.84 +/- 4.59 pmol per 10(9) platelets at day 14 in comparison with the initial value (6.87 +/- 2.25 pmol). The platelet aggregability was significantly suppressed at various time intervals but no additive or synergistic inhibitory effect by the combined administration was noted. In conclusion, the combined administration of BPT/CLZ is safe at doses used in the study, though the beneficial clinical effect of the combined administration has yet to be elucidated.
authors.affiliation: Department of Surgery II, Osaka University Medical School, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Fujitani
authors.forename: J
authors.initials: J
authors.lastname: Kambayashi
authors.forename: K
authors.initials: K
authors.lastname: Murata
authors.forename: Y
authors.initials: Y
authors.lastname: Yano
authors.forename: K
authors.initials: K
authors.lastname: Shinozaki
authors.forename: M
authors.initials: M
authors.lastname: Yukawa
authors.forename: M
authors.initials: M
authors.lastname: Sakon
authors.forename: T
authors.initials: T
authors.lastname: Murata
authors.forename: T
authors.initials: T
authors.lastname: Kawasaki
authors.forename: E
authors.initials: E
authors.lastname: Shiba
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects; D000077407:Cilostazol; D003094:Collagen / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood / Q000378:metabolism; D011464:Epoprostenol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D006261:Headache / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D013777:Tetrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; C048081:beraprost; D003094:Collagen; D011464:Epoprostenol; D000242:Cyclic AMP; D000077407:Cilostazol