Pharmacodynamic and pharmacological effects of nipradilol (K-351) in healthy volunteers. Comparison with propranolol.:Comparison with Propranolol
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The pharmacodynamic and pharmacological effects of nipradilol (K-351) were studied in a cross-over double blind fashion with propranolol as reference drug, using healthy adult male volunteers. They received orally 6 mg and 12 mg of nipradilol and 20 mg of propranolol.<BR>1) The sitting blood pressure at rest was continously lowered both for systolic blood pressure (SBP) and diastolic blood pressure (DBP). Heat rate (HR) was transiently reduced.<BR>2) No influence was seen on blood pressure or heart rate under the condition of postural change by 50°tilting.<BR>3) Both elevated SBP and increased heart rate due to a submaximal exercise load were suppressed.<BR>4) The time-course of plasma concentration of nipradilol accorded with the one compartment model. The plasma concentration of nipradilol reached to the peak at 1.5 hours after dosing. The plasma concentration of denitro-nipradilol, the main metabolite, was approximately 2 times that of nipradilol.<BR>5) The half life of elimination was approximately 6 hours.<BR>6) The plasma concentration of nipradilol correlated significantly with the reduction rate [%R] <SUB>HR</SUB> in exercise-induced tachycardia and the suppressive rate [%I] <SUB>SBP</SUB>in exercise-induced elevation of SBP. The time-course in [%R] <SUB>HR</SUB> almost corresponded to that in the plasma concentration, which suggested that nipradilol had a long-duration effect.<BR>7) [%R] HR was dose-dependent. Beta-blocking potency of nipradilol was considered to be 5 or 6 times that of propranolol.<BR>8) There were no subjective complaints except for slight drowsiness seen in one case each in the 6 and 12 mg dosings. There were no abnormalities regarding pulmonary function or the laboratory investigation tests.
- 一般社団法人 日本臨床薬理学会の論文
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