The Plasma Concentration Profiles and Pharmacokinetics of Levetiracetam among Thai Adult Patients Undergoing Intermittent Hemodialysis
Wongsakorn Promken¹,², Daraporn Rungprai³,⁴, Juthathip Suphanklang³,⁴, Pasiri Sithinamsuwan⁵, Wichai Santimaleeworagun³,⁶, Pharanwit Anundilokrit⁵,⁷
Affiliation : ¹ The College of Pharmacotherapy of Thailand, The Pharmacy Council, Nonthaburi, Thailand, ² Department of Pharmacy, Sakaeo Crown Prince Hospital, Sakaeo, Thailand, ³ Department of Pharmaceutical Care, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand, ⁴ Silpakorn University Research and Development Group in Pharmaceutical Care (SURP), ⁵ Division of Neurology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand, ⁶ Antibiotic Optimization and Patient Care Project by Pharmaceutical Initiative for Resistant Bacteria and Infectious Diseases Working Group (PIRBIG), ⁷ Regional Health Promotion Center 9th Nakhon Ratchasima, Department of health, Ministry of Public health, Nakhon Ratchasima, Thailand
Background: Levetiracetam is a second-generation antiepileptic drug that is primarily eliminated in urine via glomerular filtration and requires dose adjustment in patients with renal insufficiency. However, there are still a lack of evidence on pharmacokinetics including dialysis clearance of levetiracetam among patients undergoing intermittent hemodialysis.
Objective: To assess the plasma concentrations and pharmacokinetic parameters of levetiracetam in patients undergoing intermittent hemodialysis.
Materials and Methods: A pharmacokinetic study was conducted on six Thai adult patients receiving intermittent hemodialysis. The patients received levetiracetam 1,000 to 1,500 mg administered by intravenous injection once daily. Blood samples were obtained prior to hemodialysis, during the hemodialysis session, and post-hemodialysis to investigate levetiracetam pharmacokinetic parameters in each phase of treatments.
Results: Five of six patients had residual urine volume of more than 50 mL/day. The Pharmacokinetic parameters derived from the present study were as followed, the median dialysis clearance was 9.07 L/hour (IQR 7.13, 12.17), the median elimination rate constant (Ke) was 0.30 hour⁻¹ (IQR 0.24, 0.56), and the median elimination halflife (t½) during hemodialysis session was 2.34 hours (IQR 1.25, 2.91). The present study found the median percentage of levetiracetam plasma concentration reduction after four hours of hemodialysis was 76.89% (IQR 69.02, 85.43). Overall, plasma concentration of levetiracetam was decreased during intermittent hemodialysis sessions.
Conclusion: The findings of the present study support the use of LEV dosing of 1,000 to 1,500 mg/day and a supplemental dose after each hemodialysis session should be considered. Levetiracetam dose reduction in patients undergoing intermittent hemodialysis will lead to subtherapeutic plasma concentrations. Levetiracetam plasma concentration should be monitored in patients receiving intermittent hemodialysis.
Received 4 April 2022 | Revised 5 July 2022 | Accepted 18 July 2022
DOI: 10.35755/jmedassocthai.2022.11.13708
Keywords : Levetiracetam; Hemodialysis; Pharmacokinetics; Antiepileptic drug
