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Cancer Chemotherapy and Pharmacology

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01-08-2008 | Original Article

The first case of phenytoin intoxication associated with the concomitant use of phenytoin and TS-1, a combination preparation of tegafur, gimeracil, and oteracil potassium

Authors: Aiko Tsuda, Junshin Fujiyama, Akiko Miki, Satoko Hori, Hisakazu Ohtani, Yasufumi Sawada

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2008

Abstract

Purpose

We reported the first case of phenytoin intoxication due to the concomitant use of phenytoin and TS-1, together with a review of the literature regarding the occurrence of phenytoin intoxication due to the concomitant use of phenytoin and fluoropyrimidine antitumor drugs such as fluorouracil (5-FU) and tegafur (FT).

Methods

We showed the clinical course of our patient. Reports of phenytoin intoxication due to the concomitant use of phenytoin and fluoropyrimidine antitumor drugs in the English and Japanese language literature up to 2007 were identified by searching Medline and ICHUSHI Web (Japana Centra Revuo Medicina).

Results

A patient taking phenytoin and TS-1, a combination preparation of tegafur, gimeracil, and oteracil potassium, experienced lightheadedness and repeated falls associated with an increase in serum phenytoin concentration (32.8 μg/ml) at 1 month after the start of TS-1 treatment. The time lag between initiation of combined treatment and onset of adverse symptoms suggests the presence of an indirect mechanism, rather than direct inhibition of drug-metabolizing enzymes by drugs in TS-1 or their active metabolites.

Conclusions

Plasma phenytoin concentration should be closely monitored in patients receiving TS-1 and phenytoin concomitantly.

Afsar A, Lee C, Riddick DS (1996) Modulation of the expression on constitutive rat hepatic cytochrome P450 isozymes by 5-fluorouracil. Can J Physiol Pharmacol 74:150–156PubMedCrossRef

Brickell K, Porter D, Thompson P (2003) Phenytoin toxicity fluoropyrimidines (5FU/capecitabine): three case reports. Br J Cancer 89:615–616PubMedCrossRef

Ethical Drug package insert of Futraful capsule (Taiho Pharmaceutical Co., Ltd., Tokyo, Japan)

Fukami T, Nakajima M, Higashi E, Yamanaka H, Sakai H, McLeod HL, Yokoi T (2005) Characterization of novel CYP2A6 polymorphic alleles (CYP2A6*18 and CYP2A6*19) that affect enzymatic activity. Drug Metab Dispos 33:1202–1210PubMedCrossRef

Gilbar PJ, Brodribb TR (2001) Phenytoin and fluorouracil interaction. Ann Pharmacother 35:1367–1370PubMedCrossRef

Hara T, Ichinomiya A, Matsushima M et al (1992) A case of acute phenytoin toxicity associated with antitumor drug tegafur. Kyushu J Neuropsychiatry 38:36–41 (in Japanese)

Harada H, Rin E, Sato T (1990) Acute phenytoin toxicity due to drug interaction with antitumor drug 5-FU. J Tottori Med Assoc 18:197–199 (in Japanese)

Ikeda M, Furukawa H, Imamura H et al (2002) Pharmacokinetic study of S-1, a novel oral fluorouracil antitumor agent in animal model and in patients with impaired renal function. Cancer Chemother Pharmacol 50:25–32PubMedCrossRef

Konishi H, Morita K, Minouchi T et al (2002) Probable metabolic interaction of doxifluridine with phenytoin. Ann Pharmacother 36:831–834PubMedCrossRef

10.

Loscher W (2007) Drug transporters in the epileptic brain. Epilepsia 48(Suppl)1:8–13PubMedCrossRef

11.

Mann MW, Pons G (2007) Various pharmacogenetic aspects of antiepileptic drugtherapy. CNS Drugs 21(2):143–164PubMedCrossRef

12.

Nakai S, Yanai I (2000) Two cases of acute phenytoin toxicity probably due to drug interactions with antitumor drugs. Jpn J Clin Psychiatry 29:413–417 (in Japanese)

13.

Park JY, Kim KA (2003) Inhibitory effect of 5-fluorouracil on human cytochrome P(450) isoforms in human liver microsomes. Eur Clin Pharmacol 59:407–409CrossRef

14.

Richens A (1979) Clinical pharmacokinetics of phenytoin. Clin Pharmacokinet 4(3):153–169PubMedCrossRef

15.

Rosemergy I, Findlay M (2002) Phenytoin toxicity as a result of 5-fluorouracil administration. N Z Med J 115:U124PubMed

16.

Shirasaka T, Nakano K, Takechi T, Satake H, Uchida J, Fujioka A, Saito H, Okabe H, Oyama K, Takeda S, Unemi N, Fukushima M (1996) Antitumor activity of 1 M tegafur–0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1) against human colon carcinoma orthotopically implanted into nude rats. Cancer Res 56:2602–2606PubMed

17.

Stupans I, Richards DA, McClure MT (1995) Effects of 5-fluorouracil treatment on rat liver microsomal enzymes. Xenobiotica 25:1–8PubMedCrossRef

18.

Taguchi T, Inuyama Y, Kanamaru R, Hasegawa K, Akazawa S, Niitani H, Furue H, Kurihara M, Ota K, Suga S, Ariyoshi Y, Takai S, Shimoyama T, Toge T, Takashima S, Sugimachi K, Hara Y, Fujita H, Kimura K, Saito T, Tsukagoshi S, Nakao I (1997) Phase I study of S-1. S-1 study group Gan To Kagaku Ryoho 34(15):2253-2264

19.

Tsuchishita Y, Hori T, Kameda T, Fujimura Y, Kusumoto M (2007) A case of therapeutic drug monitoring (TDM) of phenytoin during oral treatment with tegafur. Jpn J Ther Drug Monit 24(1):47–50 (in Japanese)

20.

Wakisaka S, Shimauchi M, Kaji Y, Nonaka A, Kinoshita K (1990) Acute phenytoin toxicity associated with the antineoplastic agent UFT. Fukuoka Igaku Zasshi 81:192–196 (in Japanese)PubMed

21.

Yamamoto K, Shirakawa O, Nishiguchi N, Maeda K (2000) A case of phenytoin toxicity due to the combination treatment with tegafur. Jpn J Clin Psychopharmacol 3:263–266 (in Japanese)

22.

Yokoyama F, Nagao M, Aikawa H et al (1994) A case of acute phenytoin toxicity associated with the antitumor agent UFT. Bull Tokyo Psychiatr Assoc 1(12):49–53 (in Japanese)

Title: The first case of phenytoin intoxication associated with the concomitant use of phenytoin and TS-1, a combination preparation of tegafur, gimeracil, and oteracil potassium
Authors: Aiko Tsuda
Junshin Fujiyama
Akiko Miki
Satoko Hori
Hisakazu Ohtani
Yasufumi Sawada
Publication date: 01-08-2008
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 3/2008
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-007-0621-6

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Abstract

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