title: Pharmacokinetics of Single Ascending Doses and Multiple Doses of 20(S)-Ginsenoside Rg3 in Chinese Healthy Volunteers.
abstract: OBJECTIVE
  20(S)-Ginsenoside Rg3 could significantly inhibit tumor growth and metastasis in animals and in in vitro tumor cell invasion. This first-in-human pharmacokinetic study investigated the pharmacokinetics of 20(S)-ginsenoside Rg3 (hip intramuscular injection) in healthy Chinese volunteers.
  
  
  METHODS
  Study 1 investigated single, ascending intramuscular doses of 10-60 mg of 20(S)-ginsenoside Rg3 in 24 healthy adults; study 2 evaluated multiple intramuscular doses of 30 mg of 20(S)-ginsenoside Rg3 administered for 15 days in 9 healthy adults.
  
  
  RESULTS
  In both studies, 20(S)-ginsenoside Rg3 was rapidly absorbed, with a time to reach maximum plasma concentration (Tmax) of 4 h. After single-dose administration, elimination half-life t½was 32.0 ± 26.7, 51.7 ± 15.4 and 53.9 ± 25.7 h; maximum plasma concentration (Cmax) was 135.4 ± 35.3, 162.1 ± 47.2 and 399.8 ± 217.0 ng/mL; area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC0-∞) was 3474.1 ± 1312.3, 8156.5 ± 1782.7 and 25,666.8 ± 9401.1 ng·h/mL; clearance CL/F was 3.2 ± 0.9, 3.8 ± 0.7 and 2.7 ± 1.3 L/h; urine excretion percentage during 72 h was 0.5 ± 0.1, 0.4 ± 0.1 and 0.4 ± 0.2 % after 10, 30 and 60 mg 20(S)-ginsenoside Rg3, respectively. After multiple-dose administration, Cmaxwas 457.0 ± 165.7 and 770.2 ± 275.4 ng/mL; AUC0-48hwas 10,530.0 ± 4073.9 and 16,871.3 ± 6939.3 ng·h/mL after the first and the last 20(S)-ginsenoside Rg3 doses, respectively; fluctuation percentage was 183.0 ± 46.3 %. Accumulation ratio was 1.7 ± 0.6 at steady state.
  
  
  CONCLUSIONS
  20(S)-ginsenoside Rg3 was generally well tolerated. In these studies, 20(S)-ginsenoside Rg3 exhibited a pharmacokinetic profile suitable for once-every-2-days dosing.
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 41 Damuchang, Xicheng District, 100032, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Institute of Frontier Medical Science of Jilin University, Changchun, 130021, China.
authors.forename: Pingya
authors.initials: P
authors.lastname: Li
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 41 Damuchang, Xicheng District, 100032, Beijing, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 41 Damuchang, Xicheng District, 100032, Beijing, China. pei.hu.pumc@aol.com.
authors.forename: Pei
authors.initials: P
authors.lastname: Hu
mesh_terms: D065567:Absorption, Physiological; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D002081:Buttocks; D002681:China; D015331:Cohort Studies; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D036145:Ginsenosides / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D007273:Injections, Intramuscular; D008297:Male; D008657:Metabolic Clearance Rate; D065667:Renal Elimination; D015203:Reproducibility of Results; D014556:Urine / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D007155:Immunologic Factors; C097367:ginsenoside Rg3