It was uncovered to stimulate cytochrome P450 enzyme and thus reduce the plasma level of a wide range of conventional drugs including warfarin, voriconazole, verapamil, talinolol, tacrolimus, simvastatin, quazepam, oral contraceptives, omeprazole, nifedipine, midazolam, methadone, mephenytoin
, ivabradine, irinotecan, indinavir, imatinib, gliclazide, fexofenadine, erythromycin, digoxin, debrisoquine, ciclosporin, chlorzoxazone, atorvastatin, amitriptyline, and alprazolam [114-116].
The activation of the biguanide antimalarial proguanil co-segregates with the mephenytoin
oxidation polymorphism--a panel study.
A novel transversion in the intron 5 donor splice junction of CYP2C19 and a sequence polymorphism in exon 3 contribute to the poor metabolizer phenotype for the anticonvulsant drug s mephenytoin
. J Pharmacol Exp Ther.
Hydroxylation polymorphisms of debrisoquine and mephenytoin
in European populations.
Gram, "Pharmacokinetics of citalopram in relation to the sparteine and the mephenytoin
oxidation polymorphisms," Therapeutic DrugMonitoring, vol.
Sun exposure appears to be an exacerbating factor in otherwise predisposed individuals.3 Melasma- like hyperpigmentation has been observed in patients taking phenytoin or mephenytoin
. Melasma appears to be a chronic process that is exacerbated by sunlight and artificial UVA and UVB.
Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin
. J Pharmacol Exp Ther 1998; 286 : 1490-5.
Once the metabolism of dextromethorphan was established to cosegregate with that of debrisoquin and other prototype substrates of CYP2D6, it was unanimously accepted as an attractive alternative to the other phenotyping probes (15) because of its recognized safety, its worldwide availability, and its specificity to CYP2D6 since no co-inheritance between mephenytoin
and dextromethorphan metabolism was found in human subjects.
* Agents that occasionally cause myelosuppression (chloramphenicol, gold compounds, arsenic, sulfonamides, mephenytoin
, trimethodione, phenylbutazone, quinacrine, indomethacin, diclofenac, felbamate)
Classification and Pharmacologic Management of Seizures Seizure First Line Agents New/Alternative Agents Simple Partial phenytoin primidone carbamazepine phenobarbital valproic acid gabapentin lamotrigine felbamate topiramate ethotoin mephenytoin
Complex partial phenytoin primidone carbamazepine valproic acid phenobarbital mephobarbital gabapentin lamotrigine felbamate topiramate amobarbital Absence clonazepam methsuximide ethosuximide phensuximide valproic acid lamotrigine trimethadione Myoclonic valproic acid clonazepam Tonic Clonic phenytoin/fosphenytoin phenobarbital carbamazepine primidone valproic acid topiramate Stares epilepticus phenytoin/fosphenytoin diazepam lorazepam phenobarbital diazepam secobarbital pentobarbital
The first PM of mephenytoin
, a probe drug for CYP2C19, was reported by Kupfer et al in 19792.
The first-generation AEDs known to cause birth defects and other developmental toxicities include the hydantoins (ethotoin [Peganone], fosphenytoin [Cerebyx], mephenytoin
[Mesantoin], and phenytoin [Dilantin]), phenobarbital, primidone (Mysoline), carbamazepine (Tegretol), and valproic acid derivatives (Depakene, Depakote).