Mephenytoin

Another anticonvulsant, formerly used as a hypnotic, is 5-ethyl-5-phenyIhydantoin [631 -07-2] (Nirvanol, Mephenytoin). Its S isomer is stereo-selectively eliminated in most subjects, a fact having clinical consequences with both desired and untoward effects (119). 

Fig. 2-18. Normal phase retention of the first eluted and seeond eluted enantiomer of mephenytoin on vaneomyein CSP (250 x 4.6 mm). The flow rate was 1.0 mL min at ambient temperature (23 °C).

Armstrong and Jin [15] reported the separation of several hydrophobic isomers (including (l-ferrocenylethyl)thiophenol, 1 -benzylnornicotine, mephenytoin and disopyramide) by cyclodextrins as chiral selectors. A wide variety of crown ethers have been synthesized for application in enantioselective liquid membrane separation, such as binaphthyl-, biphenanthryl-, helicene-, tetrahydrofuran and cyclohex-anediol-based crown ethers [16-20]. Brice and Pirkle [7] give a comprehensive overview of the characteristics and performance of the various crown ethers used as chiral selectors in liquid membrane separation. 

Cytochrome P450 2C19, also termed S-mephenytoin hydroxylase, is a mixed-function oxidase localized in the endoplasmic reticulum which is responsible for the biotransformation of S-mephenytoin, some barbiturates, almost all proton pump inhibitors such as omeprazole, diazepam and others. 

Cj H7N 140-29-4) see Azatadine Dicycloverine Disopyramide Ethoheptazine Isoaminile Levocabastine Mephenytoin Methylphenidate Methylphenobarbital Milnacipran hydrochloride Oxeladin Pentapiperide Pentoxyverine Pethidine Phenglutarimide Pheniramine Phenobarbital Tolazoline Triamterene Valethamate bromide 1 -benzy l-4-cyanopiperidine (C]3H 9N2 62778-37-4) see Ketanserin... 

CgHjNO 105-07-7) see Hydroxystilbamidine isethionate a-cyanobenzeneacetam ide (C9H11N2O 771-84-6) see Mephenytoin 4-cyanobenzoic acid... 

CjHioOj 105-58-8) see Ambuside Bisoprolol Fenspiride Flurbiprofen Furazolidone Ketoprofen Mephenytoin Nifuratel Pheno barbital Pranoprofen Protizinic acid Temafloxacin Toloxatone Tybamate Zolmitriptan... 

C2H5Br 74-96-4) see Actinoquinol Amobarbital Benzilonium bromide Cyclobarbital Edrophonium chloride Heptabarb Mephenytoin Methylphenobarbital Norfloxacin Oxitropium bromide Phenobarbital Remoxipride Secbutabaibital Valdetamide ethyl bromoacetate... 

Ci)H f 0 93-55-0) see Amfeprainone Dextropropoxyphene Eprazinone Mephenytoin Phendimetrazine Phenmetrazine Phenylpropanolamine Tamoxifen... 

CNNa 143-33-9) see Alclofenac Alpidem Amphetaminil Atorvastatin calcium Azatadine Calcium pantothenate Carnitine Clopidogrel hydrogensulfate Clortermine Dexrazoxane Diclofenac Diloxanide Edetic acid Epinastine hydrochloride Ethosuximide Ethotoin Fenoprofen Ibuprofen Irbesartan Ketoprofen Lonazolac Mephenytoin Mepindolol Montelukast sodium Nabilone Oxymetazoline Paramethadione Pentorex Saquinavir Suprofen Thiamphenicol Tolmetin Trimazosin Zolpidem sodium cyanoborohydride... 

CYP2C19 is another example of the existence of both cross-ethnic and inter-individual variations in drug metabolism. This enzyme is involved in the metabolism of many psychotropics such as diazepam and tertiary tricyclic antidepressants, as well as one of the selective serotonin re-uptake inhibitors (SSRIs), citalopram. Using S-mephenytoin as the probe, previous studies showed that up to 20% of East Asians (Chinese, Japanese, and Koreans) are PMs, when only 3-5%... 

Goldstein, J. A., Ishizaki, T. etal. (1997). Frequencies ofthe defective CYP2C19 alleles responsible for the mephenytoin poor metabolizer phenotype in various Oriental, Caucasian, Saudi Arabian and American black populations. Pharmacogenetics, 7(1), 59-64. 

Xie, H. G., Stein, C. M. et al. (1999). Allelic, genotypic and phenotypic distributions of S-mephenytoin 4 -hydroxylase (CYP2C19) in healthy Caucasian populations of European descent throughout the world. Pharmacogenetics, 9(5), 539-49. 

Daniel, H. I. Edeki, T. I. (1996). Genetic polymorphism of S-mephenytoin 4 -hydroxylation. Psychopharmacol. Bull, 32, 219-30. 

Inoue, K. et al. (1997). Relationship between CYP2C9 and 2C19 genotypes and tolbutamide methyl hydroxylation and S-mephenytoin 4 -hydroxylation activities in livers of Japanese and Caucasian populations. Pharmacogenetics, 7, 103-13. 

Roh, H. K. etal. (1996). Debrisoquine and S-mephenytoin hydroxylation phenotypes and genotypes in a Korean population. Pharmacogenetics, 6, 441-7. 

CYP2D6 TCAs, SSRIs, haloperidol, mirtazepine, zuclopenthoxil, venlafaxine, sertraline CYP2C19 TCAs, mephenytoin, diazepam, moclobemid, venlafaxine... 

Bertilsson, L., Lou, Y. Q., Du, Y. L. et al. (1992). Pronounced differences between native Chinese and Swedish populations in the polymorphic hydroxylations of debrisoquin and S-mephenytoin. Clin. Pharmacol. Ther., 51, 338-97. 

Nakamura, K., Goto, F., Ray, W. A. etal. (1985). Interethnic differences in genetic polymorphism of debrisoquine and mephenytoin hydroxylation between Japanese and Caucasian populations. Clin. Pharmacol. Ther., 10,402-8. 

Andersson T, Regardh CG, Dahl-Puustinen ML, Bertilsson L. Slow omeprazole metabolizers are also poor S-mephenytoin hydroxylators. Ther Drug Monit 1990 12[4] 415-416. 

Xie HG, Kim RB, Stein CM, Wilkinson GR, Wood AJJ. Genetic polymorphism of (S)-mephenytoin 4 -hydroxylation in populations of African descent. Br J Clin Pharmacol 1999 48 402-408. 

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