Pharmacokinetics of nipradilol (K-351), a new antihypertensive agent, in human.
スポンサーリンク
概要
- 論文の詳細を見る
The Pharmacokinetics of nipradilol (K-351: 3, 4-dihydro-8-(2-hydroxy-3-iso propylamino) propoxy-3-nitroxy-2H-1-benzopyran; NIP), a new potent antihyperten sive and antianginal agent, were investigated in healthy volunteers after single or repeated oral administration.<BR>After administration at single doses of 1mg to 24mg, NIP was rapidly absorbed, reaching a maximum plasma concentration (C<SUB>max</SUB>) at 2hr, and then eliminated with a plasma half-life (T<SUB>1/2</SUB>) of 3.7 hr, irrespective of the dose. C<SUB>max</SUB> and area under the plasma levels-time curve (AUC) of NIP, as well as the amounts of NIP and its metabolites excreted in the urine increased in proportion to the dose administered. The apparent volume of distribution, systemic availability, renal clearance, and plasma clearance were 5.621/kg, 35%, 0.181/min, and 1.041/min, respectively, independent of the dose.<BR>Upon multiple oral administration of 6 mg two times daily for one or seven days, the experimental plasma concentrations of NIP and denitrated NIP coincided well with the simulation curves. Furthermore, T<SUB>1/2</SUB> values calculated from the plasma and urinary excretion rate did not differ significantly during repeated dosing, indicating no accumulation in the body.<BR>The amount of parent drug excreted into the urine was 6.3%. The major urinary metabolites arose from three metabolic pathways, namely, denitration, hydroxylation of the ring system and glucuronidation of NIP. Degradation of the isopropylaminopropanol side chain was a minor route.
著者
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Kato Kazuzo
The Cadiovascular Institute
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Yoshimura Mitsuo
Tokyo Research Laboratories Kowa Co. Ltd.
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Kojima Junji
Tokyo New Drug Research Laboratories Kowa Company Ltd.
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ITO TERUFUMI
Tokyo Research Laboratories, Kowa Co., Ltd.
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SUZUKI JUNNOSUKE
Tokyo Research Laboratories, Kowa Co., Ltd.
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Ito Terufumi
Tokyo Research Laboratories Kowa Co. Ltd.
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YOSHIMURA MITSUO
Tokyo Research Laboratories, Kowa Co., Ltd.
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KOJIMA JUNJI
Tokyo Research Laboratories, Kowa Co., Ltd.
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TSUTSUI Sueharu
Laboratory of Psychosomatic Medicine, Toho University School of Medicine
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