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Use of the Biopharmaceutics Drug Disposition Classification System (BDDCS) to Help Predict the Occurrence of Idiosyncratic Cutaneous Adverse Drug Reactions Associated with Antiepileptic Drug Usage.

Publication ,  Journal Article
Chan, R; Wei, C-Y; Chen, Y-T; Benet, LZ
Published in: AAPS J
May 2016

Cutaneous adverse reactions (CARs) from antiepileptic drugs (AEDs) are common, ranging from mild to life-threatening, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The identification of subjects carrying the HLA-B*15:02, an inherited allelic variant of the HLA-B gene, and the avoidance of carbamazepine (CBZ) therapy in these subjects are strongly associated with a decrease in the incidence of carbamazepine-induced SJS/TEN. In spite of the strong genetic associations, the initiation of hypersensitivity for AEDs is still not very well characterized. Predicting the potential for other AEDs to cause adverse reactions will be undoubtedly beneficial to avoid CARs, which is the focus of this report. Here, we explore the use of the Biopharmaceutics Drug Disposition Classification System (BDDCS) to distinguish AEDs associated with and without CARs by examining the binding relationship of AEDs to HLA-B*15:02 and data from extensive reviews of medical records. We also evaluate the lack of benefit from a Hong Kong population policy on the effects of screening for HLA-B*15:02 and previous incorrect structure-activity hypotheses. Our analysis concludes that BDDCS class 2 AEDs are more prone to cause adverse cutaneous reactions than certain BDDCS class 1 AEDs and that BDDCS Class 3 drugs have the lowest levels of cutaneous adverse reactions. We propose that BDDCS Class 3 AEDs should be preferentially used for patients with Asian backgrounds (i.e., Han Chinese, Thai, and Malaysian populations) if possible and in patients predisposed to skin rashes.

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Published In

AAPS J

DOI

EISSN

1550-7416

Publication Date

May 2016

Volume

18

Issue

3

Start / End Page

757 / 766

Location

United States

Related Subject Headings

  • Stevens-Johnson Syndrome
  • Pharmacology & Pharmacy
  • Humans
  • HLA-B Antigens
  • Carbamazepine
  • Biopharmaceutics
  • Asian People
  • Anticonvulsants
  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chan, Rosa, Chun-Yu Wei, Yuan-Tsong Chen, and Leslie Z. Benet. “Use of the Biopharmaceutics Drug Disposition Classification System (BDDCS) to Help Predict the Occurrence of Idiosyncratic Cutaneous Adverse Drug Reactions Associated with Antiepileptic Drug Usage.AAPS J 18, no. 3 (May 2016): 757–66. https://doi.org/10.1208/s12248-016-9898-x.
Journal cover image

Published In

AAPS J

DOI

EISSN

1550-7416

Publication Date

May 2016

Volume

18

Issue

3

Start / End Page

757 / 766

Location

United States

Related Subject Headings

  • Stevens-Johnson Syndrome
  • Pharmacology & Pharmacy
  • Humans
  • HLA-B Antigens
  • Carbamazepine
  • Biopharmaceutics
  • Asian People
  • Anticonvulsants
  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences