Benidipine hydrochloride--a new calcium-channel blocker of the dihydropyridine type. Pharmacokinetics, pharmacodynamics, tolerance and dose finding in mild to moderate hypertension.
(+/-)-(R*)-2,6-Dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3, 5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) is a newly synthetized calcium-channel blocker of the dihydropyridine type. In a phase I study with increasing single doses a statistically significant increase of the heart rate in supine and upright position as well as statistically significant decrease of the blood pressure in upright position was observed in healthy volunteers 1.5-6 h after application of 24 mg of KW-3049. Subsequently, in a placebo-controlled comparison in healthy volunteers the pulse rate in supine position increased statistically significantly on day 1 from 61.0 b/min (placebo) after application of 2 x 8 mg of KW-3049 to 67.4 b/min. After application of 2 x 10 mg of nifedipine the supine pulse rate increased to 63.3 b/min. The difference from placebo was not significant. At days 2-5 the pulse rate in upright position was always increased vs. placebo 3 h after application of KW-3049 and 1 h after application of nifedipine. As already observed in preclinical data, the mild onset of action with KW-3049 was also confirmed in these clinical phase I studies. Drug-induced effects on ergometric and psychomotoric parameters in healthy volunteers were mild, as expected, and due to aliquote dosages of 2 x 8 mg of KW-3049 and 2 x 10 mg of nifedipine only slightly different.(ABSTRACT TRUNCATED AT 250 WORDS)
Maier-Lenz
H
H
Institute for Clinical Pharmacology Biodesign GmbHa, Freiburg/Brsg. Fed. Rep. of Germany.
Rode
H
H
Lenau
H
H
Thieme
G
G
Wölke
E
E
Kobayashi
H
H
Kobayashi
S
S
Oka
T
T
D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004341:Drug Evaluation; D004361:Drug Tolerance; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D011187:Posture; D011674:Pulse / Q000187:drug effects
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; C050883:benidipine hydrochloride; D009543:Nifedipine