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KMID : 0391020130210010052
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Journal of Korean Society for Clinical Pharmacology and Therapeutics
2013 Volume.21 No. 1 p.52 ~ p.62
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A Randomized, Placebo Controlled, Double Blind, Parallel Group, Multiple Dosing, Dose Escalation Clinical Study to Evaluate Pharmacokinetics/Pharmacodynamics and Tolerability of Zofenopril in Healthy Korean Subjects
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Oh Jae-Seong
Lee Seung-Hwan
Lim Kyoung-Soo
Chung Jae-Yong
Shin Sang-Goo
Jang In-Jin
Yu Kyung-Sang
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Abstract
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Background :Zofenopril is a new Angiotensin Converting Enzyme (ACE) inhibitor for the treatment of the patients with hypertension and congestive heart failure. This study aimed to evaluate the pharmacokinetics (PKs)/pharmacodynamics (PDs) and tolerability of zofenopril in healthy Korean subjects.
Methods :A randomized, double blind, placebo-controlled, multiple dosing parallel group study with two dosage groups (zofenopril 30 mg or 60 mg) was conducted in healthy Korean male subjects. Each dosage group consisted of 10 subjects and they were randomly assigned to receive zofenopril or placebo with a ratio of 4:1. PK characteristics of zofenopril and its active metabolite, zofenoprilat, were evaluated after single or multiple dosing. Serum ACE activities and blood pressures were measured for PD evaluation. Adverse events, clinical laboratory tests, electrocardiograms, vital signs and physical examinations were performed for tolerability evaluation.
Results :The PK characteristics of zofenopril and zofenoprilat after single dose and multiple doses were similar to one another. The metabolic ratio of zofenoprilat to zofenopril after single dose and multiple doses were 12.4 and 14.9, respectively, in the 30 mg dosage group, and were 6.8 and 6.6, respectively, in the 60 mg dosage group. Complete serum ACE activity inhibition was observed within 1 hour in both doses but it was maintained longer in the 60 mg dosage group compared to the 30 mg dosage group. There were no clinically significant abnormalities in tolerability evaluations.
Conclusion : The PK/PD characteristics of zofenopril and zofenoprilat after single or multiple administrations were explored. Zofenopril was well tolerated after multiple administrations in healthy Korean subjects.
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KEYWORD
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Zofenopril, Zofenoprilat, ACE inhibitor, Pharmacokinetics, Pharmacodynamics
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