title: Effect of Long-term Topiramate Therapy on Serum Bicarbonate and Potassium Levels in Adult Epileptic Patients.
abstract: BACKGROUND
  Topiramate (TPM) is a sulfamate-substituted monosaccharide that is structurally different from other antiepileptic drugs. TPM inhibits carbonic anhydrase activity, which is associated with loss of bicarbonate from the kidney and consequently metabolic acidosis or electrolyte imbalance.
  
  
  OBJECTIVE
  The objectives of the study were to investigate the influence of TPM therapy on bicarbonate and potassium levels in adult epileptic patients.
  
  
  METHODS
  Data were collected from 59 adult patients on monotherapy or co-therapy of TPM and other antiepileptic drugs. Serum bicarbonate and potassium levels were available from all patients. Steady-state TPM trough concentrations were determined in blood samples by high-performance liquid chromatography. Data analysis was performed by SPSS software (version 17, Chicago, IL).
  
  
  RESULTS
  Patients were divided into group A (duration of therapy shorter than or equal to 5 years) and group B (duration of therapy longer than 5 years). Significant difference (P < 0.05) in serum bicarbonate levels was observed between these 2 groups. Bicarbonate levels were linearly related to the TPM therapy duration. No correlation was found between the TPM dose or patient age and bicarbonate or potassium levels, as well as between therapy duration and potassium level. Linear regression analysis showed no significant association among 54 available TPM trough concentrations and bicarbonate or potassium levels.
  
  
  CONCLUSIONS
  Results highlight the frequent occurrence of lower bicarbonate level associated with prolonged TPM therapy. Monitoring bicarbonate levels in patients on long-term TPM therapy might be useful.
authors.affiliation: Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade - Faculty of Pharmacy, Belgrade, Serbia marijaj@pharmacy.bg.ac.rs.
authors.forename: Marija
authors.initials: M
authors.lastname: Jovanović
authors.affiliation: Clinic of Neurology, Clinical Centre of Serbia, Belgrade, Serbia University of Belgrade - Faculty of Medicine, Belgrade, Serbia.
authors.forename: Dragoslav
authors.initials: D
authors.lastname: Sokić
authors.affiliation: Department of Biopharmaceutics and Pharmacokinetics, University of Ljubljana - Faculty of Pharmacy, Ljubljana, Slovenia.
authors.forename: Iztok
authors.initials: I
authors.lastname: Grabnar
authors.affiliation: Department of Pharmacology, Clinical Pharmacology and Toxicology, University of Belgrade - Faculty of Medicine, Belgrade, Serbia.
authors.forename: Milica
authors.initials: M
authors.lastname: Prostran
authors.affiliation: Centre of Medical Biochemistry, Clinical Centre of Serbia, Belgrade, Serbia.
authors.forename: Radmila
authors.initials: R
authors.lastname: Obrenović
authors.affiliation: Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade - Faculty of Pharmacy, Belgrade, Serbia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Vučićević
authors.affiliation: Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade - Faculty of Pharmacy, Belgrade, Serbia.
authors.forename: Branislava
authors.initials: B
authors.lastname: Miljković
keywords: acid base balance; adult medicine; adverse drug reactions; electrolytes; epilepsy