Effect of propranolol on pharmacokinetics of clozapine in schizophrenic patients: a meta-analysis

Xiding Yang; Qiangyong Yan; Lingfeng Yang; Jingjing Li; Xiao Fan; Jindong Chen; Haishan Wu; Yongyu Yang; Ronghua Zhu; Pingfei Fang

doi:10.1007/s00228-024-03690-w

Effect of propranolol on pharmacokinetics of clozapine in schizophrenic patients: a meta-analysis

Eur J Clin Pharmacol. 2024 Apr 19. doi: 10.1007/s00228-024-03690-w. Online ahead of print.

Authors

Xiding Yang^{1

2}, Qiangyong Yan^{1

2}, Lingfeng Yang^{2

3}, Jingjing Li^{1

2}, Xiao Fan^{1

2}, Jindong Chen⁴, Haishan Wu⁴, Yongyu Yang⁵, Ronghua Zhu^{6

7}, Pingfei Fang^{8

9}

Affiliations

¹ Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
² Phase I Clinical Trial Center, The Second Xiangya Hospital of Central South University, Changsha, China.
³ Department of Metabolism & Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
⁴ Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, China.
⁵ Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China. yongyuyang@csu.edu.cn.
⁶ Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China. ubillow@csu.edu.cn.
⁷ Phase I Clinical Trial Center, The Second Xiangya Hospital of Central South University, Changsha, China. ubillow@csu.edu.cn.
⁸ Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China. fangpingfei@csu.edu.cn.
⁹ Phase I Clinical Trial Center, The Second Xiangya Hospital of Central South University, Changsha, China. fangpingfei@csu.edu.cn.

PMID: 38639762
DOI: 10.1007/s00228-024-03690-w

Abstract

Purpose: Clozapine is the effective therapy for treatment-refractory schizophrenia. However, the use of clozapine is limited by its adverse effects. As propranolol is frequently used for the prevention and treatment of clozapine-induced tachycardia, we performed a meta-analysis to evaluate the effects of propranolol on steady state pharmacokinetics of clozapine in schizophrenic patients.

Methods: We included 16 retrospective studies on the effects of propranolol on steady state pharmacokinetics of clozapine in schizophrenic patients, with data from both generic and brand name treatment phases in eight clozapine bioequivalence studies conducted in a single center in China from 2018 to 2022. Review Manager 5.4 was used for meta-analysis of the included studies.

Results: The SMDs with 95% CIs of AUC_0-12, C_max,ss, C, and C were calculated to be 0.44 (0.23, 0.64), 0.40 (0.20, 0.61), 0.43 (0.22, 0.63), and 0.44 (0.23, 0.64), respectively. These findings proved that combination with propranolol would increase the systemic exposure of clozapine. T_1/2 of clozapine was significantly longer in the presence of propranolol than in the absence of propranolol (SMD = 0.32, 95% CI [0.12, 0.52], p = 0.002). There was no statistically significant difference for T of clozapine in the presence or absence of propranolol (SMD = - 0.05, 95% CI [- 0.25, 0.15], p = 0.63).

Conclusion: The combination with propranolol could significantly increase systemic exposure and extended T_1/2 of clozapine, and thus need to be considered in prescribing decisions.

Keywords: Clozapine; Drug interaction; Meta-analysis; Pharmacokinetic; Propranolol.