Affiliation:
1. Department of Pharmacy, Chongqing University Cancer Hospital, Chongqing, China
2. Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens, NY, United States
Abstract
Background:
Cyclophosphamide is approved for the treatment of a variety of tumors,
yet the use of cyclophosphamide is limited by kidney and liver toxicity. In the clinic, the Wuzhi
capsule is approved to attenuate cyclophosphamide toxicity in the kidney and liver.
Objective:
We aimed to investigate the effects of the principal ingredients of Wuzhi capsule,
schisandrin A (SIA) and schisantherin A (STA), on the pharmacokinetics of cyclophosphamide.
Methods:
The essential pharmacokinetic data and physicochemical parameters of SIA, STA, and
cyclophosphamide were collected. Physiologically based pharmacokinetic (PBPK) models of SIA,
STA, and cyclophosphamide were built in Simcyp Simulator and verified using published clinical
pharmacokinetic data. The verified PBPK models were used to predict potential herb-drug interactions
(HDIs) between cyclophosphamide and SIA and STA in cancer patients.
Results:
The area under the plasma concentration–time curve (AUC) of cyclophosphamide was increased
by 18% and 1% when co-administered with STA and SIA at a single dose, respectively,
and increased by 301% and 29% when co-administered with STA and SIA at multiple doses, respectively.
The maximum concentration (Cmax) of cyclophosphamide was increased by 75% and
7% when co-administered with STA and SIA at multiple doses, respectively.
Conclusion:
The AUC and Cmax of cyclophosphamide were increased when cyclophosphamide was
combined with the Wuzhi capsule, compared to cyclophosphamide alone. Our study shows that the
adverse drug reactions and toxicity of cyclophosphamide should be closely monitored and an effective
dosage adjustment of cyclophosphamide may need to be considered when co-administered
with the Wuzhi capsule.
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology (medical),Cancer Research,Drug Discovery,Oncology,General Medicine
Cited by
4 articles.
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