Pharmacokinetics of Single Ascending Doses and Multiple Doses of 20(S)-Ginsenoside Rg3 in Chinese Healthy Volunteers

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. 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. In both studies, 20(S)-ginsenoside Rg3 was rapidly absorbed, with a time to reach maximum plasma concentration (T (max)) of 4 h. After single-dose administration, elimination half-life t (A 1/2) was 32.0 +/- A 26.7, 51.7 +/- A 15.4 and 53.9 +/- A 25.7 h; maximum plasma concentration (C (max)) was 135.4 +/- A 35.3, 162.1 +/- A 47.2 and 399.8 +/- A 217.0 ng/mL; area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC(0-a)) was 3474.1 +/- A 1312.3, 8156.5 +/- A 1782.7 and 25,666.8 +/- A 9401.1 ng center dot h/mL; clearance CL/F was 3.2 +/- A 0.9, 3.8 +/- A 0.7 and 2.7 +/- A 1.3 L/h; urine excretion percentage during 72 h was 0.5 +/- A 0.1, 0.4 +/- A 0.1 and 0.4 +/- A 0.2 % after 10, 30 and 60 mg 20(S)-ginsenoside Rg3, respectively. After multiple-dose administration, C (max) was 457.0 +/- A 165.7 and 770.2 +/- A 275.4 ng/mL; AUC(0-48h) was 10,530.0 +/- A 4073.9 and 16,871.3 +/- A 6939.3 ng center dot h/mL after the first and the last 20(S)-ginsenoside Rg3 doses, respectively; fluctuation percentage was 183.0 +/- A 46.3 %. Accumulation ratio was 1.7 +/- A 0.6 at steady state. 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.