Pharmacokinetic Basis for Using Saliva Matrine Concentrations as a Clinical Compliance Monitoring in Antitumor B Chemoprevention Trials in Humans

Dinh Bui, Lenora A. McWilliams, Lei Wu, Haiying Zhou, Stuart J. Wong, Ming You, Diana S.L. Chow, Rashim Singh, Ming Hu

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

This study reports the first clinical evidence of significantly high secretion of matrine in a multi-component botanical (Antitumor B, ATB) into human saliva from the systemic circulation. This is of high clinical significance as matrine can be used as a monitoring tool during longitudinal clinical studies to overcome the key limitation of poor patient compliance often reported in cancer chemoprevention trials. Both matrine and dictamine were detected in the saliva and plasma samples but only matrine was quantifiable after the oral administration of ATB tablets (2400 mg) in 8 healthy volunteers. A significantly high saliva/plasma ratios for Cmax (6.5 ± 2.0) and AUC0–24 (4.8 ± 2.0) of matrine suggested an active secretion in saliva probably due to entero-salivary recycling as evident from the long half-lives (t1/2 plasma = 10.0 ± 2.8 h, t1/2 saliva = 13.4 ± 6.9 h). The correlation between saliva and plasma levels of matrine was established using a population compartmental pharmacokinetic co-model. Moreover, a species-relevant PBPK model was developed to adequately describe the pharmacokinetic profiles of matrine in mouse, rat, and human. In conclusion, matrine saliva concentrations can be used as an excellent marker compound for mechanistic studies of active secretion of drugs from plasma to saliva as well as monitor the patient’s compliance to the treatment regimen in upcoming clinical trials of ATB.

Original languageEnglish (US)
Article number89
JournalCancers
Volume15
Issue number1
DOIs
StatePublished - Dec 23 2022

Keywords

  • OCT transporter
  • PBPK modeling
  • cancer chemoprevention
  • entero-salivary recycling
  • patient compliance tracker
  • pharmacokinetics
  • plasma-saliva correlation
  • saliva excretion marker

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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