Qian Zhao1, Pingya Li2, Ji Jiang1, Pei Hu3. 1. 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. 2. Institute of Frontier Medical Science of Jilin University, Changchun, 130021, China. 3. 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.
Abstract
BACKGROUND AND OBJECTIVES: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 (T max) of 4 h. After single-dose administration, elimination half-life t ½ was 32.0 ± 26.7, 51.7 ± 15.4 and 53.9 ± 25.7 h; maximum plasma concentration (C max) 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, C max was 457.0 ± 165.7 and 770.2 ± 275.4 ng/mL; AUC0-48h was 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.
RCT Entities:
BACKGROUND AND OBJECTIVES: 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 (T max) of 4 h. After single-dose administration, elimination half-life t ½ was 32.0 ± 26.7, 51.7 ± 15.4 and 53.9 ± 25.7 h; maximum plasma concentration (C max) 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, C max was 457.0 ± 165.7 and 770.2 ± 275.4 ng/mL; AUC0-48h was 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.