| Summary: | 博士 === 國立陽明大學 === 傳統醫藥研究所 === 107 === Introduction: Hepatitis and chronic liver disease have been a sequelae healthcare problem worldwide including Taiwan. Patients having chronic hepatitis may be treated with diuretics spironolactone while compensative cirrhosis develops. Artemisia capillaris Thunb (Yin-Cen-Hao), Gardenia jasminoides Ellis (Zhi-Zi), and Rheum officinale Baill (Da-Huang) were a combined formulation intended to deal with hepatitis and jaundice. Researches have proved it with anti-hepatic fibrosis, anti-hepatic apoptosis, and alleviation of hepatic oxidative stress effects in bile duct ligation rats. However, herb-drug interactions of this common available herbal formula products could be a priority safety issue for the patient with the chronic liver disease under conventional diuretic treatment. The purpose of the study was aimed to discover the herb-drug interactions between the herbal formula Yin-Chen-Hao-Tang (YCHT) and diuretic drugs spironolactone, to guarantee the quality, safety, and efficacy of commonly used natural products.
Material and methods: Selective high-performance liquid chromatography (HPLC) and HPLC tandem mass spectrometry (HPLC-MS/MS) methods were developed and validated for simultaneous determination of the bioactive compounds, scoparone, geniposide and rhein in YCHT and for diuretic spironolactone and metabolite canrenone, respectively. The interaction study was collecting urine sample after oral administrated with spironolactone (20 mg/kg, p.o.) with or without the pretreatment of pharmaceutical products YCHT (1 g/kg/day or 3 g/kg/day p.o.) for 5 days. The interaction experiments were performed in both normal and common bile duct ligation (CBDL) rats. Pharmacokinetic parameters of urine including cumulative amounts, excretion rate, the area under the rate curve (AURC), and terminal elimination half-life (t1/2) of spironolactone, as well as pharmacodynamics data of urine weight and volume, urinary sodium and potassium concentration, and sodium to potassium (Na+ / K+) ratio were acquired.
Results: The interaction experiment combined the pharmacokinetic and pharmacodynamic results showed a significant raising in the cumulative amount and AURC of the metabolite canrenone under pretreatment of high dose YCHT. Meanwhile, the decrease of Na+ / K+ ratio in YCHT 3 g/kg group was noted accompanying with the increased potassium elimination. Besides, the significant decrease of the cumulative amount of canrenone, mean excretion rate, and area of rate curve in urine was discovered in the pretreatment of high dose YCHT in common bile duct ligation (CBDL) rats. The urine weight and volume were decreased significantly but not in urinary Na+ / K+ ratio under the high dose of YCHT.
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