This review briefly discusses the use of capillary electrophoretic (CE) methods for the investigations of different aspects of pharmacokinetics. In most investigations, CE was the method of choice because of its unique features, including high resolving power for chiral or metabolite separation, small sample volume for pediatric pharmacokinetics or for cell-based investigations, in situ microdialysis sampling for rapid eliminations, low UV wavelength detection for nonderivatized analytes, fast and simplified sample processing for existing methods that require tedious sample preparation, or as a second method for verifications. Moreover, instrumental aspects of CE-based assays for pharmacokinetic studies, such as different modes of CE methods for analyzing biological samples, sample stacking for increasing detection sensitivity, and coupling techniques with microdialysis and mass spectrometry, are also discussed in this review. Furthermore, the advantages and limitations of CE methods as well as the future outlook for pharmacokinetic studies are summarized.

01 Apr 1997·Journal of Chromatography B: Biomedical Sciences and Applications

Investigation of the stereoselective in vitro metabolism of the chiral antiasthmatic/antiallergic drug flezelastine by high-performance liquid chromatography and capillary zone electrophoresis

Article

Author: G. Blaschke ; J. Engel ; M. Locher ; H.O. Borbe ; S. Paris

An achiral HPLC method using a silica gel column as well as two independent chiral analytical methods by HPLC and capillary zone electrophoresis (CZE) were developed in order to investigate the in vitro metabolism of the racemic antiasthmatic/antiallergic drug flezelastine. The chiral HPLC analysis was performed on a Chiralpak AD column, which also allowed the simultaneous separation of the N-dephenethyl metabolite. The chiral separation by CZE was achieved by the addition of beta-cyclodextrin to the run buffer. The stereoselectivity of the in vitro biotransformation of flezelastine was investigated using liver homogenates of different species. Depending on the species, diverse stereoselective aspects were demonstrated. The determination of the enantiomeric ratios of flezelastine and of N-dephenethylflezelastine after incubations of racemic flezelastine with liver microsomes revealed that porcine liver microsomes showed the greatest enantioselectivity of the biotransformation. (-)-Flezelastine was preferentially metabolized. After incubations with bovine liver microsomes the enantiomer of N-dephenethylflezelastine formed from (+)-flezelastine dominated. Incubations of the pure enantiomers of flezelastine with induced rat liver microsomes resulted in the stereoselective formation of a hitherto unknown metabolite, which was only detected in samples of (+)-flezelastine. Initial structure elucidation of the compound indicated that the new metabolite was most likely an aromatically hydroxylated derivative of the N-dephenethylflezelastine.

01 Jul 1995·Biochemical PharmacologyQ2 · MEDICINE

Azelastine and flezelastine as reversing agents of multidrug resistance: Pharmacological and molecular studies

Q2 · MEDICINE

Article

Author: Jacques Robert ; Hu Yan Ping

The effects of two new phthalazinone derivatives, azelastine (AZ) and flezelastine (FZ), on the reversal of resistance to doxorubicin (dox) were studied using two variants of the rat C6 glioblastoma cell line, selected with dox (C6 0.5) or with vincristine (C6 1V). Both lines presented a multidrug-resistant phenotype which was, in the case of C6 0.5 cells, likely to be accompanied by an additional mechanism leading to intracellular tolerance of the drug. Both AZ and FZ reversed dox resistance in a concentration-dependent manner, and FZ was shown to be at least three times more potent than AZ. FZ was able, at a relatively high concentration (30 microM), to completely restore dox sensitivity in both cell lines. Both drugs were able to virtually restore dox accumulation to the level reached in sensitive cells, and, interestingly, this complete restoration occurred at lower concentrations of modulator than required for complete reversal of resistance. FZ was able to reverse dox intracellular tolerance of C6 0.5 cells and to restore dox accumulation at the IC50 to the level observed in sensitive cells. AZ and FZ both inhibited azidopine binding to membrane preparations of C6 0.5 and C6 1V cells, although FZ was more potent. Both drugs more successfully inhibited azidopine binding to membranes prepared from C6 1V cells (which express the mdr1b gene product) than to membranes from C6 0.5 cells (which express the mdr1a gene product). In view of its potent activity on MDR, further preclinical evaluation of FZ is warranted.

100 Deals associated with Flezelastine hydrochloride

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Indication	Highest Phase	Country/Location	Organization	Date
Asthma	Phase 2	-	Asta Medica Ltda	-
Asthma	Phase 2	Germany	ASTA Medica AG	-
Neoplasms	Phase 2	Germany	ASTA Medica GmbH	-
Neoplasms	Phase 2	United States	-	-
Rhinitis, Allergic	Phase 2	-	Asta Medica Ltda	-

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