Effect of nebicapone on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects.
Nebicapone is a new catechol-O-methyltransferase inhibitor. In vitro, nebicapone has showed an inhibitory effect upon CYP2C9, which is responsible for the metabolism of S-warfarin. The objective of this study was to investigate the effect of nebicapone on warfarin pharmacokinetics and pharmacodynami...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 64; no. 10; pp. 961 - 967 |
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| Autores principales: | , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Springer Nature
Oct2008
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105557644&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105557644 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Oct2008 vid: 64 iid: 10 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 105557644 2010055823 10.1007/s00228-008-0534-2 NLM18679669 105557644 ppf: 961 ppct: 6 formats: fmt: @attributes: type: P tig: atl: Effect of nebicapone on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. aug: au: Almeida L Falcão A Vaz-da-Silva M Nunes T Santos A Rocha J Neta C Macedo T Fontes-Ribeiro C Soares-da-Silva P sug: subj: Warfarin Pharmacodynamics Analysis of Variance Descriptive Statistics Funding Source International Normalized Ratio Parkinson Disease Therapy Pharmacy and Pharmacology Warfarin Blood Human ab: Nebicapone is a new catechol-O-methyltransferase inhibitor. In vitro, nebicapone has showed an inhibitory effect upon CYP2C9, which is responsible for the metabolism of S-warfarin. The objective of this study was to investigate the effect of nebicapone on warfarin pharmacokinetics and pharmacodynamics in healthy subjects. Single-centre, open-label, randomised, two-period crossover study in 16 healthy volunteers. In one period, subjects received nebicapone 200 mg thrice daily for 9 days and a racemic warfarin 25-mg single dose concomitantly with the nebicapone morning dose on day 4 (test). In the other period, subjects received a racemic warfarin 25-mg single dose alone (reference). The treatment periods were separated by a washout of 14 days. For R-warfarin, mean +/- SD C[max] was 1,619 +/- 284 ng/mL for test and 1,649 +/- 357 ng/mL for reference, while AUC[0-t] was 92,796 +/- 18,976 ng·h/mL (test) and 73,597 +/- 11,363 ng·h/mL (reference). The R-warfarin test-to-reference geometric mean ratio (GMR) and 90% confidence interval (90%CI) were 0.973 (0.878-1.077) for C[max] and 1.247 (1.170-1.327) for AUC[0-t]. For S-warfarin, mean +/- SD C[max] was 1,644 +/- 331 ng/mL for test and 1,739 +/- 392 ng/mL for reference, while AUC[0-t] was 66,627 +/- 41,199 ng·h/mL (test) and 70,178 +/- 42,560 ng·h/mL (reference). The S-warfarin test-to-reference GMR and 90%CI were 0.932 (0.845-1.028) for C[max] and 0.914 (0.875-0.954) for AUC[0-t]. No differences were found for the pharmacodynamic parameter (INR). Nebicapone showed no significant effect on S-warfarin pharmacokinetics or on the coagulation endpoint (INR). A mild inhibition of the R-warfarin metabolism was found but is unlikely to be of clinical relevance. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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