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AAPS PharmSciTech

, 20:247 | Cite as

The Pharmacokinetic Prediction of Cyclosporin A after Coadministration with Wuzhi Capsule

  • Jingjing Fan
  • Lu Chen
  • Xiaoqing Lu
  • Mengxue Li
  • Liqin ZhuEmail author
Research Article
  • 18 Downloads

Abstract

We aim to describe the influence of principal ingredients of Wuzhi capsule, schisandrin A (SIA) and schisantherin A (STA), on the pharmacokinetics of cyclosporin A (CsA) and to quantify the herb–drug interactions (HDIs) between SIA, STA, and CsA. CsA is a first-line immunosuppressant for anti-rejection therapy after solid organ transplantation, while narrow therapeutic window associated with strong hepatotoxicity largely limited its use. Wuzhi capsule, a liver-protective drug, was approved for coadministration with CsA to reduce the hepatotoxicity. There are few studies exploring HDIs of CsA when coadministered with Wuzhi capsule. The essential adjusted physicochemical data and pharmacokinetic parameters of SIA, STA, and CsA were collected. Then physiologically based pharmacokinetic (PBPK) models of SIA, STA, and CsA were built and verified in healthy subjects using Simcyp respectively. The refined PBPK models were used to estimate potential HDIs between CsA and SIA, STA. The simulated plasma concentration–time curves of CsA, SIA, and STA were in good accordance with the observed profiles respectively. CsA pharmacokinetics were improved after coadministration. After a single dose and multiple doses, the area under the plasma concentration–time curve (AUC) of CsA was increased by 47% and 226% when coadministered with STA, respectively, and by 8% and 36% when coadministered with SIA, respectively. PBPK models sufficiently described the pharmacokinetics of CsA, SIA, and STA. Compared with SIA, STA inhibited CsA metabolism to a greater extent. Our result revealed the dose of CsA can be reduced to maintain similar profile when used concomitantly with Wuzhi capsule.

KEY WORDS

cyclosporin A Wuzhi capsule herb–drug interactions PBPK 

Notes

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with Ethical Standards

Conflict of Interest

None.

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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Jingjing Fan
    • 1
  • Lu Chen
    • 2
  • Xiaoqing Lu
    • 2
  • Mengxue Li
    • 2
  • Liqin Zhu
    • 1
    • 2
    • 3
    Email author
  1. 1.Graduate CollegeTianjin University of Traditional Chinese MedicineTianjinChina
  2. 2.Pharmaceutical CollegeTianjin Medical UniversityTianjinChina
  3. 3.Department of PharmacyTianjin First Central HospitalTianjinChina

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