Document Detail

Metabolic acidosis with topiramate and zonisamide: an assessment of its severity and predictors.
MedLine Citation:
PMID:  21278619     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Carbonic anhydrase (CA) inhibitors topiramate and zonisamide can induce metabolic acidosis in some patients. Our aims were to assess the prevalence and severity of this acidosis and to determine its predictors.
METHODS: For 70 patients established on treatment with topiramate (n=55) or zonisamide (n=14) or both (n=1), we measured electrolytes, and genotyped single nucleotide polymorphisms (SNPs) in the main renal CA isoenzymes (II, IV and XII).
RESULTS: Twenty-six percent of patients had a metabolic acidosis (serum bicarbonate <20 mmol/l). The mean serum bicarbonate of patients taking topiramate was significantly lower than those taking zonisamide (P=0.002). We found no association between serum bicarbonate and the dose of drug or the duration of treatment. Serum bicarbonate levels were associated with the CA type XII SNPs rs2306719 (P=0.006 by one-way analysis of variance) and rs4984241 (P=0.015), but this association was not strong enough to survive correction for multiple testing.
CONCLUSION: The development of acidosis with topiramate and zonisamide is not determined by drug dose or by treatment duration, but may be influenced by polymorphisms in the gene for CA type XII. The aforementioned SNPs lie 9.8 kb apart in intron 1 of the CA type XII gene, and deserve further study in a larger cohort of patients.
Nasir S Mirza; Ana Alfirevic; Andrea Jorgensen; Anthony G Marson; Munir Pirmohamed
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pharmacogenetics and genomics     Volume:  21     ISSN:  1744-6880     ISO Abbreviation:  Pharmacogenet. Genomics     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-04-13     Completed Date:  2011-08-03     Revised Date:  2013-08-21    
Medline Journal Info:
Nlm Unique ID:  101231005     Medline TA:  Pharmacogenet Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  297-302     Citation Subset:  IM    
Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
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MeSH Terms
Acid-Base Equilibrium / drug effects
Acidosis, Renal Tubular / chemically induced,  epidemiology*,  genetics*
Carbonic Anhydrase Inhibitors / adverse effects*,  therapeutic use
Carbonic Anhydrases / genetics*
Epilepsy / drug therapy*
Fructose / adverse effects,  analogs & derivatives*,  therapeutic use
Genome-Wide Association Study
Isoxazoles / adverse effects*,  therapeutic use
Middle Aged
Polymorphism, Single Nucleotide
Severity of Illness Index
Young Adult
Reg. No./Substance:
0/Carbonic Anhydrase Inhibitors; 0/Isoxazoles; 0H73WJJ391/topiramate; 30237-26-4/Fructose; 68291-97-4/zonisamide; EC Anhydrases; EC anhydrase XII

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