Kinetics and dynamics of the peripheral neurokinin-1 receptor antagonist SLV317 in healthy individuals

• Verfasst von: Hesse, Christiane [VerfasserIn]
• Verfasst von: Luntz, Steffen P. [VerfasserIn]
• Verfasst von: Siedler, Heike [VerfasserIn]
• Verfasst von: Unnebrink, Kristina [VerfasserIn]
• Verfasst von: Mikus, Gerd [VerfasserIn]
• Verfasst von: Bruijn, Marianne [VerfasserIn]
• Verfasst von: Zondag, Edu [VerfasserIn]
• Verfasst von: Vries, Michiel [VerfasserIn]
• Verfasst von: Seibert-Grafe, Monika [VerfasserIn]
• Verfasst von: Haefeli, Walter E. [VerfasserIn]
• Titel: Kinetics and dynamics of the peripheral neurokinin-1 receptor antagonist SLV317 in healthy individuals
• Verf.angabe: Christiane Hesse, Steffen P. Luntz, Heike Siedler, Kristina Unnebrink, Gerd Mikus, Marianne de Bruijn, Edu Zondag, Michiel de Vries, Monika Seibert‐Grafe & Walter E. Haefeli
• E-Jahr: 2006
• Jahr: 24 January 2006
• Umfang: 6 S.
• Fussnoten: Gesehen am 17.05.2021
• Titel Quelle: Enthalten in: British journal of clinical pharmacology
• Ort Quelle: Oxford : Wiley-Blackwell, 1974
• Jahr Quelle: 2006
• Band/Heft Quelle: 61(2006), 4, Seite 414-419
• ISSN Quelle: 1365-2125
• DOI: doi:10.1111/j.1365-2125.2006.02590.x
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: neurokinin-1 receptor antagonist
• Sach-SW: pharmacokinetics
• Sach-SW: SLV317
• Sach-SW: substance P
• Sach-SW: vein
• K10plus-PPN: 1757916059

Abstract

Aims To investigate the pharmacokinetics and the pharmacodynamic effects in dorsal hand veins of the neurokinin-1 receptor antagonist SLV317. Methods In a randomized, double-blind, placebo-controlled cross-over study 19 healthy men received a single oral dose of SLV317 or placebo. Blood samples were collected for analysis of SLV317 plasma concentrations and the inhibition of the venodilator response to substance P was evaluated using the hand vein compliance method. Results Administration of 250 mg SLV317 as an oral solution was well tolerated and resulted in mean peak plasma concentrations (± SEM) of 77 ± 9 ng ml−1 within 47 ± 3 min; the mean half-life was 9.9 ± 1.6 h. In hand veins preconstricted with phenylephrine, local infusion of substance P resulted in a mean venodilation of 56 ± 8% and 49 ± 6% (P = 0.91) before administration of SLV317 or placebo, respectively. SLV317 caused a substantial inhibition of substance P-induced venodilation, whereas placebo had no effect (P < 0.001). The maximum antagonizing effect of SLV317 averaged 95 ± 8% and was observed after 1.47 ± 00.24 h. Correspondingly, the mean area under the effect curve after administration of SLV317 [278 ± 67% h−1; 95% confidence interval (CI) 198, 358] was significantly higher compared with placebo (49 ± 12% h−1; 95% CI −24, 122; P < 0.001). Conclusions This study demonstrates that the neurokinin-1 receptor antagonist SLV317 is an orally active and highly effective antagonist of substance P-induced effects in humans.