Phenytoin-folate interactions: differing effects of the sodium salt and the free acid of phenytoin - PubMed

Phenytoin-folate interactions: differing effects of the sodium salt and the free acid of phenytoin

G F Carl et al. Epilepsia. 1992 Mar-Apr.

Abstract

Chronic phenytoin (PHT) treatment has long been associated with folate deficiency. It has been suggested that pH changes in the gut associated with PHT ingestion may be responsible for decreased folate uptake either by direct inhibition of folate transport into the intestinal mucosa or by inhibition of folate conjugase activity. To examine these possibilities, rats were gavaged chronically with PHT using either the sodium salt (NaPHT) or the free acid (HPHT) in the presence of folic acid as the dietary source of folate. The NaPHT caused a greater depletion of folate in the liver and brain and a significant increase in methylenetetrahydrofolate reductase activity in the liver. The HPHT caused a significantly decreased weight gain over the 8 weeks of treatment and resulted in a much higher liver PHT concentration and a slightly lower plasma PHT concentration. These data support the hypothesis that PHT-induced changes in pH in the gut affect the enterohepatic circulation of folate.

Similar articles

• Phenytoin treatment and folate supplementation affect folate concentrations and methylation capacity in rats.

  Carl GF, Smith ML, Furman GM, Eto I, Schatz RA, Krumdieck CL. Carl GF, et al. J Nutr. 1991 Aug;121(8):1214-21. doi: 10.1093/jn/121.8.1214. J Nutr. 1991. PMID: 1861170

• Phenytoin-induced depletion of folate in rats originates in liver and involves a mechanism that does not discriminate folate form.

  Carl GF, Hudson FZ, McGuire BS Jr. Carl GF, et al. J Nutr. 1997 Nov;127(11):2231-8. doi: 10.1093/jn/127.11.2231. J Nutr. 1997. PMID: 9349852

• Phenytoin-folic acid: a review.

  Rivey MP, Schottelius DD, Berg MJ. Rivey MP, et al. Drug Intell Clin Pharm. 1984 Apr;18(4):292-301. doi: 10.1177/106002808401800404. Drug Intell Clin Pharm. 1984. PMID: 6370643 Review.

• [Disorders of folate metabolism--primary and secondary metabolic disorders].

  Arakawa T. Arakawa T. Tanpakushitsu Kakusan Koso. 1972 Mar;17(3):196-202. Tanpakushitsu Kakusan Koso. 1972. PMID: 4554255 Review. Japanese. No abstract available.

Cited by

• Carbamazepine versus phenytoin monotherapy for epilepsy: an individual participant data review.

  Nevitt SJ, Marson AG, Tudur Smith C. Nevitt SJ, et al. Cochrane Database Syst Rev. 2019 Jul 18;7(7):CD001911. doi: 10.1002/14651858.CD001911.pub4. Cochrane Database Syst Rev. 2019. PMID: 31318037 Free PMC article.

• Carbamazepine versus phenytoin monotherapy for epilepsy: an individual participant data review.

  Nevitt SJ, Marson AG, Weston J, Tudur Smith C. Nevitt SJ, et al. Cochrane Database Syst Rev. 2017 Feb 27;2(2):CD001911. doi: 10.1002/14651858.CD001911.pub3. Cochrane Database Syst Rev. 2017. PMID: 28240353 Free PMC article. Updated. Review.

• Phenobarbitone versus phenytoin monotherapy for epilepsy: an individual participant data review.

  Nevitt SJ, Tudur Smith C, Marson AG. Nevitt SJ, et al. Cochrane Database Syst Rev. 2019 Jul 31;7(7):CD002217. doi: 10.1002/14651858.CD002217.pub3. Cochrane Database Syst Rev. 2019. PMID: 31425629 Free PMC article. Review.

• Phenytoin versus valproate monotherapy for partial onset seizures and generalised onset tonic-clonic seizures: an individual participant data review.

  Nolan SJ, Marson AG, Weston J, Tudur Smith C. Nolan SJ, et al. Cochrane Database Syst Rev. 2016 Apr 28;4(4):CD001769. doi: 10.1002/14651858.CD001769.pub3. Cochrane Database Syst Rev. 2016. PMID: 27123830 Free PMC article. Updated. Review.

• Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data.

  Nevitt SJ, Sudell M, Weston J, Tudur Smith C, Marson AG. Nevitt SJ, et al. Cochrane Database Syst Rev. 2017 Jun 29;6(6):CD011412. doi: 10.1002/14651858.CD011412.pub2. Cochrane Database Syst Rev. 2017. PMID: 28661008 Free PMC article. Updated. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Wiley

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information