PopPK Profile of Qishe Pill: Study Protocol for a Phase I Clinical Trial

Population Pharmacokinetic Modeling of Qishe Pill in Three Major TCM-defined Constitutional Types of Healthy Chinese Subjects: Study Protocol for a Phase I Clinical Trial

Qishe Pill (Shanghai Sundise Traditional Chinese Medicine Co., Ltd, China), composed of processed Radix Astragali, Muscone, Szechuan Lovage Rhizome, Radix Stephaniae Tetrandrae, Ovientvine, and Calculus Bovis Artifactus, has been developed and spread in use into clinical settings in 2009. As individualization has become the trend of modern medicine, a personalized medicine of Qishe Pill should be documented and practiced with various patients according to the ancient TCM system, a classification of personalized constitution type, which has been established to determine predisposition and prognosis to diseases as well as therapy and life-style administration. Therefore, we describe the population pharmacokinetic profile of Qishe Pill and compare its extent of metabolism in the 3 major Constitution Type (Qi-Deficiency, Yin-Deficiency and Blood-Stasis) to address major challenges of individualized and standardized Traditional Chinese Medicine into clinical practice.

With the greatly increased morbidity of neck pain, it brought a large challenge to some optimal therapies for various situations in population at a given time based on their demographic, physiological and pathological characteristics. Chinese proprietary herbal medicines, as a kind of Complementary and Alternative Medicine (CAM), are usually developed from some well-established and long-standing recipes and formulated as tablets or capsules for commerce, convenience or palatability. Although these advantage mentioned, a good quantification and a strict standardization in detail are still need to be improved for individualized implementation in therapeutic strategies. Based on the YQHY decoction (Yi-Qi Hua-Yu Decoction, tonify Qi and promoting circulation and removing stasis), Qishe Pill (Shanghai Sundise Traditional Chinese Medicine Co., Ltd, China) has been developed and spread in use into clinical settings in 2009. As individualization has become the trend of modern medicine, a personalized medicine of Qishe Pill should be documented and practiced with various patients according to the ancient TCM system, a classification of personalized constitution type, which has been established to determine predisposition and prognosis to diseases as well as therapy and life-style administration. Therefore, we describe the population pharmacokinetic profile of Qishe Pill and compare its extent of metabolism in the 3 major Constitution Type (Qi-Deficiency, Yin-Deficiency and Blood-Stasis) to address major challenges of individualized and standardized Traditional Chinese Medicine into clinical practice.

Inclusion

• Aged 20-35
• 18.5 kg/m2 ≤Body mass index (BMI) <23 kg/m2
• TCM-constitutionally typed as either the 3 major type

Exclusion

• History of impaired fasting glucose or diabetes mellitus (past history of diabetes or fasting blood glucose at screening ≥100 mg/dl)
• History of liver disease (hepatitis, hepatic cirrhosis) or hepatic dysfunction (AST or ALT at screening ≥40 U/L)
• History of renal dysfunction (creatinine at screening ≥1.2 mg/dl)
• History of heart disease (heart failure, angina pectoris, myocardial infarction, arrhythmia)
• History of malignant tumor
• Having digestive disorders that can interfere with normal absorption of standard diet (gastritis, gastric ulcer, duodenitis, duodenal ulcer, etc.)
• Smoking during the recent 3 months
• Alcohol consumption 3 or more times a week during the recent 3 months
• Women who were pregnant, intended to become pregnant, or breast- feeding
• Medicated during the recent month for therapeutic or prophylactic purposes
• Participating in another clinical trial