Influence of Renal Function on Pharmacokinetics of Antiepileptic Drugs Metabolized by CYP3A4 in a Patient With Renal Impairment

Therapeutic Drug Monitoring
Yoshiaki YamamotoYushi Inoue

Abstract

Several studies have demonstrated that renal impairment not only decreases renal clearance but also hepatic clearance of medications that are CYP3A4 substrates. We evaluated the influence of renal function on the pharmacokinetics of antiepileptic drugs metabolized by CYP3A4. We retrospectively calculated the concentration/dose ratio (CD ratio) for topiramate and clobazam in an epilepsy patient with renal impairment. In addition, we determined the CD ratio of perampanel in 17 patients with normal renal function and compared it with that in the patient with renal impairment. A patient with frontal lobe epilepsy and mild renal impairment [creatinine clearance (CCr): 67.7 mL/min] was taking phenytoin and 3 CYP3A4 substrates (topiramate, clobazam, and perampanel). With progression of renal impairment (CCr: 28.1 mL/min), the CD ratios of topiramate and clobazam increased by about 2-fold. The mean CD ratio of perampanel was 1740 ± 966 ng·mL·mg·kg in the 17 patients with normal renal function using phenytoin. By contrast, the CD ratio of perampanel was markedly higher (range: 5327-9113 ng·mL·mg·kg) in the patient with renal impairment (CCr: <20 mL/min). These findings suggest that dose adjustment based on therapeutic drug monitoring is...Continue Reading

References

May 1, 1992·Clinical Pharmacology and Therapeutics·Y CaracoM Levy
May 7, 2003·Clinical Pharmacology and Therapeutics·Thomas C DowlingWilliam L Henrich
Jul 10, 2008·Clinical Pharmacokinetics·Suresh MallikaarjunSteven L Bramer
Aug 10, 2010·Clinical Pharmacokinetics·Angelika WeilKarl-Heinz Molz
Jul 23, 2014·European Journal of Clinical Pharmacology·Yoshiaki YamamotoYoshiyuki Kagawa

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Citations

Feb 23, 2020·Seizure : the Journal of the British Epilepsy Association·Sherif Hanafy MahmoudS Nizam Ahmed
Feb 25, 2021·Clinical Kidney Journal·Josef Finsterer

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