フェニトインの剤形変更に伴う血清中濃度の上昇 : 症例と要因の解析  [in Japanese] An Increase in Serum Phenytoin Concentration by Changes of Dosage Form : Case Reports and Its Mechanism  [in Japanese]

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Author(s)

Abstract

Phenytoin (PHT) exhibits nonlinear pharmacokinetics in the therapeutic range. Therefore a slight increase in dose may lead to considerable elevation of the serum PHT level. Although its bioavailability is dependent on the formulation, bioequivalence is considered to be preserved between the three major formulations, of tablet, 97% fine granules, and 10% powder. However, we experienced many cases of increases serum PHT concentration after changes in formulation from 97% fine granules to 97/4% hospital-made fine granules, and from the latter to 10% powder. Retrospective analysis revealed that these alterations were accompanied by 55% and 16% increases in the serum concentration-to-dose ratio of PHT, respectively. We investigated the factors of this increase by analyzing the weight of remaining powder in a package and the PHT content of each formulation. Each package of PHT formulation prepared with 97% fine granules and 10% powder was unsealed, and the contents were weighed to calculate the rate of recovery. The rate of ingestion was estimated by correcting the rate of recovery by PHT strength (i. e., 1.0 for 10% powder and 0.97 for fine granules). The rates of recovery and ingestion for 10% powder were 13% and 16% higher than those for 97% fine granules, respectively (<i>p</i><0.01). In conclusion, Changing the PHT formulation from 97% fine granules to 10% powder may lead to a considerable increase in the serum PHT concentration and possibly induce PHT toxicity.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 122(5), 331-338, 2002-05-01

    The Pharmaceutical Society of Japan

References:  10

  • <no title>

    PLAA G. L.

    Arch. Int. Pharmacodyn. Ther. 128, 375, 1960

    Cited by (1)

  • <no title>

    BESELT R. C.

    Clin. Chem. 21, 44-62, 1975

    Cited by (1)

  • <no title>

    MASUR H.

    Neurology 39, 432-433, 1989

    Cited by (1)

  • <no title>

    BOREUS L. O.

    J. Neurol. 223, 241-249, 1980

    Cited by (1)

  • <no title>

    DAINIPPON PHARMACEUTICAL CO. Ltd

    Bioavailabilities of ALEVIATIN Fine Granules and ALEVIATIN 10% Powder

    Cited by (1)

  • <no title>

    SHIMIZU Y.

    J. Jpn. Soc. Hosp. Pharm. 30, 459-462, 1994

    Cited by (1)

  • <no title>

    EMORI K.

    Abstracts of papers, the 32nd Annual Meeting of Japan Epilepsy Society, Yokohama, 1998 127

    Cited by (1)

  • Cerebellar Atrophy After Acute Phenytoin Intoxication

    KURUVILLA Thomas , BHARUCHA N. E.

    Epilepsia 38(4), 500-502, 1997-04-01

    References (10) Cited by (3)

  • <no title>

    SHIGEMATSU M.

    J. Jpn. Soc. Hosp. Pharm. 26, 865-869, 1990

    Ichushi Web Cited by (3)

  • <no title>

    MAMIYA K.

    Epilepsia 39, 1317-1323, 1998

    DOI Cited by (3)

Cited by:  4

Codes

  • NII Article ID (NAID)
    110003648448
  • NII NACSIS-CAT ID (NCID)
    AN00284903
  • Text Lang
    JPN
  • Article Type
    Journal Article
  • ISSN
    00316903
  • NDL Article ID
    6151265
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z19-411
  • Data Source
    CJP  CJPref  NDL  NII-ELS  J-STAGE 
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