Renal Function and Hemoglobin Independently Predict Levetiracetam Exposure in Epilepsy Patients: A Multifactorial Regression Study

Xuehui Jiang,1,* Fangfang Xiong,2,* Zhihang Lin,1 Xiaowei Huang1 1Department of Pharmacy, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, People’s Republic of China; 2Department of Pharmacy, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhihang Lin, Department of Pharmacy, Quanzhou First Hospital Affiliated to Fujian Medical University, No. 1028 Anji South Road, Fengze District, Quanzhou, 362000, People’s Republic of China, Tel +86 13506000324, Email [email protected] Xiaowei Huang, Department of Pharmacy, Quanzhou First Hospital Affiliated to Fujian Medical University, No. 1028 Anji South Road, Fengze District, Quanzhou, 362000, People’s Republic of China, Tel +86 13400538528, Email [email protected]: To investigate the key factors influencing the plasma concentration of levetiracetam (LEV) in patients with epilepsy and to establish a predictive model for LEV steady-state trough concentration.Patients and Methods: Clinical data from 130 epilepsy patients (175 steady-state trough concentration blood samples) were retrospectively collected at a single center. Univariate analysis and multiple linear regression modeling were employed to systematically quantify the independent effects of demographic characteristics, biochemical indicators, and concomitant medications on the LEV C/D. The robustness of the model was validated using the Bootstrap method (1000 resamples).Results: Creatinine clearance rate (Ccr) emerged as the strongest independent predictor (unstandardized β = − 0.168, p < 0.001), with every 1 mL/min increase in Ccr resulting in a 0.168 ng·mL− 1/(g·d− 1) decrease in C/D. Hemoglobin (HGB) exhibited a secondary negative association (unstandardized β = − 0.070, p < 0.05), where every 1 g/L decrease led to a 0.070 ng·mL− 1/(g·d− 1) increase in C/D. Bootstrap validation confirmed the stability of these coefficients (95% CI: Ccr [− 0.221, − 0.123], HGB [− 0.140, − 0.008]). The final predictive equation was: C/Dpred [ng·mL− 1/(g·d− 1)] = 37.759 − 0.168 × Ccr (mL/min) − 0.070 × HGB (g/L) (adjusted R² = 0.440, p < 0.001).Conclusion: Routine clinical indicators Ccr and HGB are core influencing factors of LEV exposure. This model quantifies their independent effects on LEV steady-state trough concentration, providing novel insights into the interindividual variability of LEV pharmacokinetics and offering a potential tool for aiding individualized dosing strategies, especially in resource-limited settings where therapeutic drug monitoring is not readily available. However, its generalizability still needs to be demonstrated through subsequent external validation and prospective multicenter studies.Keywords: levetiracetam, creatinine clearance, hemoglobin, multifactorial regression, epilepsy