当前位置： SCI文献检索 > THERAPEUTIC DRUG MONITORING期刊下所有文献 > Fluconazole bioequivalence study: quantification by tandem mass spectrometry.

Fluconazole bioequivalence study: quantification by tandem mass spectrometry.

Abstract：

:To develop a new method for quantifying fluoconazole in human plasma and to compare the bioavailability of two fluconazole capsule formulations, an open, randomized, two-period crossover study with a one-week washout interval was conducted in 24 healthy volunteers. Plasma samples were obtained up to 168 hours after drug administration and the serum fluconazole concentrations were analyzed using electrospray tandem mass spectrometry coupled to liquid chromatography using multiple reaction monitoring mode. The pharmacokinetic parameters obtained for fluconazole after the administration of each formulation included the Area under the curve (AUC)(0-168h), AUC(0-infinity), Cmax, Cmax/AUC(0-168h), Tmax, elimination rate constant (Ke), and half-life (T1/2). Within- and between-run imprecision was less than 2.3% and 8.2%, respectively. Inaccuracy within and between runs was -1.5% and -9.7%, respectively. The pharmacokinetic parameters for bioequivalence showed a normal distribution, and the variance of AUC(0-168h), AUC(0-infinity), and Cmax were homoscedastic. The geometric mean for the Fluconal/Zoltec (Fluconal; Libbs Farmacêutica Ltda, São Paulo, Brazil; Zoltec; Laboratórios Pfizer Ltda., São Paulo, Brazil) individual percent ratio was 94.9% for AUC(0-168h), 94.7% for AUC(0-infinity), 80.1% for Cmax, 102.6% for Ke, 97.5% for T1/2, and 0.93 for Tmax (arithmetic mean of individual differences). We have developed a method in which liquid chromatography is coupled with electrospray tandem mass spectrometry to improve the pharmacokinetic analysis of fluconazole. Because the 90% CI AUC is within the interval proposed for the Food and Drug Administration, we concluded that Fluconal is bioequivalent to Zoltec in terms of absorption. The CV was 27.5% for the Cmax parameter, indicating that fluconazole's absorption rate is highly variable. The European Union Regulatory Agency accepts an interval of 70-143%, and because the 90% CI for Cmax is within the interval proposed for the European Union agency, we conclude that Fluconal is bioequivalent to Zoltec for the rate of absorption.

journal_name

Ther Drug Monit

journal_title

Therapeutic drug monitoring

authors

Moraes LA,Lerner FE,Moraes ME,Moraes MO,Corso G,De Nucci G

doi

10.1097/00007691-199904000-00010

subject

Has Abstract

pub_date

1999-04-01 00:00:00

pages

200-7

issue

eissn

0163-4356

issn

1536-3694

journal_volume

pub_type

临床试验,杂志文章,随机对照试验

在线工具

Fluconazole bioequivalence study: quantification by tandem mass spectrometry.