Marija Jovanović1, Dragoslav Sokić2, Iztok Grabnar3, Milica Prostran4, Radmila Obrenović5, Katarina Vučićević6, Branislava Miljković6. 1. Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade - Faculty of Pharmacy, Belgrade, Serbia marijaj@pharmacy.bg.ac.rs. 2. Clinic of Neurology, Clinical Centre of Serbia, Belgrade, Serbia University of Belgrade - Faculty of Medicine, Belgrade, Serbia. 3. Department of Biopharmaceutics and Pharmacokinetics, University of Ljubljana - Faculty of Pharmacy, Ljubljana, Slovenia. 4. Department of Pharmacology, Clinical Pharmacology and Toxicology, University of Belgrade - Faculty of Medicine, Belgrade, Serbia. 5. Centre of Medical Biochemistry, Clinical Centre of Serbia, Belgrade, Serbia. 6. Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade - Faculty of Pharmacy, Belgrade, Serbia.
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.
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 epilepticpatients. 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: Thangam Venkatesan; David J Levinthal; Sally E Tarbell; Safwan S Jaradeh; William L Hasler; Robert M Issenman; Kathleen A Adams; Irene Sarosiek; Christopher D Stave; Ravi N Sharaf; Shahnaz Sultan; B U K Li Journal: Neurogastroenterol Motil Date: 2019-06 Impact factor: 3.598