Effect of danshen extract on pharmacokinetics of theophylline in healthy volunteers

Br J Clin Pharmacol. 2008 Feb;65(2):270-4. doi: 10.1111/j.1365-2125.2007.03027.x. Epub 2007 Oct 24.

Abstract

What is already known about this subject: Danshen extract is widely used for the treatment and prevention of coronary heart disease and other diseases of senility in Asia. Danshen extract and theophylline may be prescribed together to treat patients with asthma. In human, theophylline with low therapeutic index is mainly metabolized by CYP1A2. In vitro findings have shown that human CYP1A2 is inhibited by the ethyl acetate extract of danshen and danshen pharmaceutical product. There may be drug interactions between danshen extract and theophylline (CYP1A2 substrate).

What this study adds: This study concerned drug interactions between danshen extract and theophylline in Chinese volunteers. Long-term oral intake of danshen extract does not change the basic pharmacokinetic parameters of theophylline. Dose adjustment of theophylline thus may not be necessary in patients receiving concomitant therapy with danshen extract.

Aims: To examine the potential effect of danshen extract on the pharmacokinetics of theophylline.

Methods: In a sequential cross-over study with two phases, 12 volunteers took 100 mg theophylline on day 1 and day 15. From day 2 to day 15, volunteers received danshen extract tablets three times daily, four tablets each time for 14 days. On day 15, they received four danshen extract tablets with 100 mg theophylline. Plasma concentrations of theophylline were measured on days 1 and 15 periodically for 24 h.

Results: The 90% confidence interval of C(max), t(1/2) and CL/F of theophylline with 14-day danshen extract tablets vs. without comedication were (101.42, 121.36) (84.57, 106.72) and (88.82, 105.72), respectively. The time to peak plasma theophylline concentration was unchanged by danshen (P > 0.05). The pharmacokinetics parameter of theophylline was unaffected by danshen extract.

Conclusions: Danshen extract does not influence the metabolism of theophylline in healthy volunteers. Dose adjustment of theophylline thus may not be necessary in patients receiving concurrent therapy with danshen extract tablets.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cross-Over Studies
  • Drug Interactions / physiology
  • Drugs, Chinese Herbal / pharmacokinetics*
  • Humans
  • Phenanthrolines / blood
  • Phenanthrolines / pharmacokinetics
  • Salvia miltiorrhiza*
  • Theophylline / blood
  • Theophylline / pharmacokinetics*
  • Time Factors

Substances

  • Drugs, Chinese Herbal
  • Phenanthrolines
  • dan-shen root extract
  • Theophylline