Project Title:

Animal Study on Oseltamivir with CM Formulae
奧斯他偉(特敏福)與中藥方劑的動物研究

Principal Investigator:

Professor Moses S. S. CHOW

Organization:

School of Pharmacy, The Chinese University of Hong Kong

Start Year:

2006 - 2007

Status:

Completed

Type of Study:

Research 

Summary:

Introduction

Oseltamivir (O) is currently the drug of choice for avian influenza, which represents an important health care goal in Hong Kong. The Hospital Authority (HA) Central Committee on Infectious Disease and Infection Control Branch Centre for Health Protection have jointly recommended the “western” drug oseltamivir (Tamiflu) for prophylaxis and treatment of avian influenza. In addition, a panel of the Chinese medicine experts from HA together with the Task Force on Herb-Drug Interaction Research has recommended 4 CM formulae for the prophylaxis and treatment of influenza with oseltamivir. It is expected that many Hong Kong citizens will be prescribed with such WM and CM for avian influenza if there is an outbreak. In view of lack of information on such combined usage of WM and CM, the present study aims to provide preliminary data on the potential interaction of oseltamivir in combination with 2 most recognized CM formulae (CMF1 and CMF2) for avian influenza as determined by a CM Expert Panel.

Method

Various groups of rats were set up with the combinations as follows:

  1. O alone;
  2. O+CMF1(銀翹散/桑菊飲)(at 2 different doses);
  3. O+CMF2(麻杏石甘湯+千金蘆莖葉湯)(at 2 different doses);
  4. CMF1 or CMF2 alone for duration of 5 days. CMF was treated 2 hour after O treatment. Dicholorous was added after 5-day treatment in order to prevent O hydrolysis, urine, plasma O and its active metabolite (M) concentration were then measured.

All drug concentrations were determined by a validated LC/MS/MS method.

Result

  1. Following Oseltamivir (O) + CMF1, peak plasma M concentration, area under curve (AUC), urinary recovery and metabolic ratio (AUC ratio M/O) were significantly decreased in comparison to that following O alone, and these effects appeared to be does dependent.
  2. Following O+CMF2, AUC and urinary excretion of M were decreased compared to that following O alone. No significant change in metabolic ratio was observed.
  3. The antiviral effect as represented by % plaque inhibition were significantly greater following normal doses of either O+CMF1 or O+CMF2 as compared to O alone or control. No dose dependent antiviral effect of CMF was observed.

Conclusion

Many components from CMF1 and CMF2 appear to be absorbable. It seems that concurrent administration of CMF1 at both 1.95 g/kg and 3.90 g/kg) and CMF2 at 1.55 g/kg could reduce concentration of OC in rats, the active metabolite of O after oral administration of O (30 mg/kg). The mechanism of reduction of OC by CM F1 appears to be inhibition of O absorption and metabolism (with high dose of CM F1). On the other hand, CM F2 appears to decrease mainly absorption of O leading to a lower OC concentration. These preliminary results may imply a reduction of antiviral activity after combination treatment. Further studies on the significant of the pharmacokinetic interactions in human subjects as well as antiviral effect with the combination of O and CM F1 or CM F2 are needed.
Reference:
  1. Zuo, Z., Chang, Q., Ngai, K., Chan, P., Ngan, T. M., Wong, V. T., & Chow, M. S. (2009). Herb-drug interaction involving oseltamir and Chinese medicine formulae: Pharmacokinetic and dynamic studies. Clinical Pharmacology & Therapeutics, 85, S87. (Abstract)
  2. Chow, M. S. S., Chang, Q., & Zuo, J. (2008). Herb-drug interaction involving oseltamivir and Chinese medicine formula. The FASEB Journal, 22, 1136.24. (Abstract)
  3. Chang, Q., Chow, M. S. S., & Zuo, Z. (2009). Studies on the influence of esterase inhibitor to the pharmacokinetic profiles of oseltamivir and oseltamivir carboxylate in rats using an improved LC/MS/MS method. Biomedical Chromatography, 23, 852–857.
  4. Chang Q, Wo S, Ngai KL, Wang X, Fok B, Ngan TM, Wong VT, Chan TY, Lee VH, Tomlinson B, Chan PK, Chow MS, Zuo Z (2014). Bench to bed evidences for pharmacokinetic and pharmacodynamic interactions involving oseltamivir and chinese medicine. Evid Based Complement Alternat Med. 2014:354172. doi: 10.1155/2014/354172. 

Keywords:

Chinese Medicine (CM); Herb-drug interaction; Chinese medicine formulae; Pharmacokinetic; Oseltamir; Dynamic studies; Dichlorvos; Pharmacokinetics; LC/MS/MS; Animal study

中藥; 中西藥交互作用; 中藥複方; 藥物代謝動力學; 特敏福; 二甲基二氯乙烯基磷酸酯; 動態研究; 藥物代謝動力學; 動物研究