Abstract:
OBJECTIVE:To evaluate the effect of cilostazol administration on warfarin pharmacokinetics and pharmacodynamics following a single 25 mg dose of warfarin. DESIGN:A randomised double-blind 2-period crossover with healthy volunteers receiving either 100 mg cilostazol twice daily for 13 days or matching placebo twice daily for 13 days, and the other treatment 21 days later. A single 25 mg dose of warfarin was given 14 days prior to the start of the study, and 7 days after the cilostazol and placebo treatments. STUDY PARTICIPANTS:15 normal healthy male volunteers. OUTCOME MEASURES:Noncompartmental pharmacokinetic parameters for (R)- and (S)-warfarin, the area under the curve of the prothrombin time (AUCPT), activated partial thromboplastin time (AUCaPTT), Ivy bleeding times, unbound fraction (fu) of cilostazol, and warfarin were determined for each individual. RESULTS:For (R)- and (S)-warfarin, the 90% confidence intervals for the ratios of the geometric means (90% CI) of the maximum plasma concentration and area under the plasma concentration-time curve were between 0.88 to 1.03. The 90% CI for the AUCPT and AUCaPTT was between 0.95 and 1.06. For Ivy bleeding time, the 90% CI for the ratios of the geometric means ranged between 0.71 and 1.22. The fu of cilostazol did not differ significantly between the 2 treatments. There was a 17% increase in the fu of warfarin (p < 0.05), which was not clinically significant. CONCLUSIONS:Coadministration of warfarin with twice daily administration of cilostazol 100 mg did not alter (R)- and (S)-warfarin pharmacokinetics, prothrombin time, partial thromboplastin time, Ivy bleeding times, or cilostazol protein binding.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Mallikaarjun S,Bramer SLdoi
10.2165/00003088-199937002-00009keywords:
subject
Has Abstractpub_date
1999-01-01 00:00:00pages
79-86eissn
0312-5963issn
1179-1926journal_volume
37 Suppl 2pub_type
临床试验,杂志文章,随机对照试验abstract::High dosage busulfan (1 mg/kg orally every 6 hours x 16 doses) is frequently used in preparative regimens for haemopoietic stem cell transplantation (HSCT). Busulfan is well absorbed after oral administration, exhibits low protein binding and is metabolised through conjugation with glutathione to form a thiophenium io...
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pub_type: 杂志文章,评审
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journal_title:Clinical pharmacokinetics
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199834030-00001
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journal_title:Clinical pharmacokinetics
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pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Clinical pharmacokinetics
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更新日期:2000-03-01 00:00:00