Stereoselective pharmacokinetics of flobufen in rats

Trejtnar, František; Wsól, Vladimı́r; Szotáková, Barbora; Skálová, Lenka; Pávek, Petr; Kuchař, Miroslav

doi:10.1002/(sici)1520-636x(1999)11:10<781::aid-chir7>3.0.co;2-9

Cited by 10 publications

(6 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to this result, one assumption arose: inversion of R-F to S-F or inversion of (2R;4S)-DHF to (2S;4S)-DHF, or both cases together, could increase the final amount of (2S;4S)-DHF. The inversion of R-F to S-F has been already described in rats [15] and in ruminants [16]. This type of unidirectional inversion of R enantiomers of arylpropionic acids to Senantiomers has been reported many times [17-24].…”

Section: Discussionmentioning

confidence: 80%

See 1 more Smart Citation

The stereospecificity of flobufen metabolism in isolated guinea pig hepatocytes

et al. 2003

Self Cite

View full text Add to dashboard Cite

Background: Flobufen (F) is an original nonsteroidal anti-inflammatory drug with one center of chirality. 4-Dihydroflobufen (DHF), compound with two chiral centers, is the main metabolite of F in microsomes and cytosol in all standard laboratory animals. This work describes the biotransformation of F enantiomers and DHF stereoisomers in isolated male guinea pig hepatocytes. Guinea pigs were chosen with respect to similarities in F metabolism as in Man found earlier. R-F, S-F, (2R;4S)-DHF, (2S;4R)-DHF, (2S;4S)-DHF and (2R;4R)-DHF, structurally very similar compounds, served as substrates in order to observe their interaction with enzymes. Stereospecificity of the respective enzymes was studied in vitro, using hepatocytes monolayer. Chiral HPLC using R,R-ULMO column as chiral stationary phase was used for detection and quantitation of metabolites.

show abstract

Section: Discussionmentioning

confidence: 80%

“…Inversion of S-F to R-F or inversion of (2S;4S)-DHF to (2R;4S)-DHF or combination of both of them must be taken into account. Inversion of S-F to R-F has already been suspected in rats [15]. Bi-directional inversions of ibuprofen and ketoprofen have already been described in both guinea pigs [27] and mice [28].…”

Section: Discussionmentioning

confidence: 99%

The stereospecificity of flobufen metabolism in isolated guinea pig hepatocytes

et al. 2003

Self Cite

View full text Add to dashboard Cite

show abstract

“…83,84 In rats 85 and humans, 86 benoxaprofen showed stereospecific inversion from R-to S-enantiomer with high inversion rate in rats than humans. Trejtnar et al 87 discussed the chiral inversion of flobufen [4-(2 0 , 4 0 -difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid] in male wistar rat, after administration of racemic mixture and individual enantiomers of the drug. The authors reported the ratio of S/R enantiomer as 13.3 after racemic flobufen administration.…”

Section: In Vivo Racemizationmentioning

confidence: 99%

“…Rapid changes in S/R enantiomer concentration ratio within first minute after racemic flobufen administration in rat 87. …”

mentioning

confidence: 97%

Role of racemization in optically active drugs development

et al. 2007

View full text Add to dashboard Cite

U.S. Food and Drug Administration issues certain guidelines for marketing of optically active drugs as some enantiomers racemize into human body, leading to the generation of other antipodes, which may be toxic or ballast to the human beings. Moreover, racemization reduces the administrated dosage concentration as optically active enantiomer converted into its inactive counter part. Therefore, the study of racemization of such type of drugs is an important and urgent need of today. This article describes in vitro and in vivo racemization of optically active drugs. The racemization process of various optically active drugs has been discussed considering the effect of different variables i.e. pH, temperature, concentration of the drug, ionic concentration, etc. Attempts have also been made to discuss the mechanisms of racemization. Besides, efforts have been made to suggest the safe dosages of such type of drugs too.

show abstract

“…In rats [91] and humans [92], benoxaprofen showed stereospecific inversion from R-to S-enantiomer with a higher inversion rate in rats than in humans. Trejtnar et al [93] discussed the chiral inversion of flobufen [4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid] in male Wistar rats, after administration of racemic mixture and individual enantiomers of the drug. The authors reported a ratio of S/R enantiomers as 13.3 after racemic flobufen administration.…”

Section: In Vivo Racemizationmentioning

confidence: 99%

Homochiral Drug Design and Development by Racemization

Ali

2007

CCHTS

View full text Add to dashboard Cite

One of the enantiomers of a racemic drug may be pharmacologically inactive or toxic or ballast and, hence, U.S. FDA and European agencies have issued certain guidelines for marketing of optically active (homochiral) drugs. However, some homochiral drug enantiomers racemize in to human body leading to the generation of other antipodes, which may be toxic or ballast to the human beings. In addition, racemization reduces the administrated dosage concentration when the optically active enantiomer is converted into its inactive form. Therefore, racemization studies of homochiral drugs are the important and urgent need of today. This article reviews in vitro and in vivo racemization of homochiral drugs. The racemization of some homochiral drugs is described considering the affect of different variables such as temperature, concentration of the drug, ionic concentration, pH, addition of cyclodextrins, formation of inclusion complexes, etc. Efforts have also been made to discuss the mechanisms of the racemization process. Attempts have been made to suggest safe dosages of such drugs.

show abstract

Stereoselective pharmacokinetics of flobufen in rats

Cited by 10 publications

References 19 publications

The stereospecificity of flobufen metabolism in isolated guinea pig hepatocytes

The stereospecificity of flobufen metabolism in isolated guinea pig hepatocytes

Role of racemization in optically active drugs development

Homochiral Drug Design and Development by Racemization

Contact Info

Product

Resources

About