Yamamoto Yoshiaki, Usui Naotaka, Nishida Takuji, Mori Miho, Takahashi Yukitoshi, Imai Katsumi, Kagawa Yoshiyuki, Inoue Yushi
Department of Clinical Research, National Epilepsy Center, NHO, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
Department of Clinical Pharmaceutics, Graduate School of Pharmaceutical Sciences University of Shizuoka, Shizuoka, Japan.
Ther Drug Monit. 2018 Feb;40(1):144-147. doi: 10.1097/FTD.0000000000000461.
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 probably necessary when topiramate, clobazam, or perampanel is prescribed for patients with moderate-to-severe renal impairment.
