Zhao Qian, Li Pingya, Jiang Ji, Hu Pei
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.
Institute of Frontier Medical Science of Jilin University, Changchun, 130021, China.
Eur J Drug Metab Pharmacokinet. 2016 Dec;41(6):845-853. doi: 10.1007/s13318-015-0304-3.
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 ) of 4 h. After single-dose administration, elimination half-life t was 32.0 ± 26.7, 51.7 ± 15.4 and 53.9 ± 25.7 h; maximum plasma concentration (C ) 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 (AUC) 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 was 457.0 ± 165.7 and 770.2 ± 275.4 ng/mL; AUC 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.
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.
20(S)-人参皂苷Rg3可显著抑制动物肿瘤生长和转移以及体外肿瘤细胞侵袭。这项首次人体药代动力学研究考察了20(S)-人参皂苷Rg3（臀部肌肉注射）在健康中国志愿者中的药代动力学。
研究1在24名健康成年人中考察了单次递增肌肉注射10 - 60mg的20(S)-人参皂苷Rg3；研究2在9名健康成年人中评估了多次肌肉注射30mg的20(S)-人参皂苷Rg3，给药15天。
在两项研究中，20(S)-人参皂苷Rg3吸收迅速，达血浆最大浓度（T ）的时间为4小时。单剂量给药后，消除半衰期t 分别为32.0 ± 26.7、51.7 ± 15.4和53.9 ± 25.7小时；血浆最大浓度（C ）分别为135.4 ± 35.3、162.1 ± 47.2和399.8 ± 217.0ng/mL；血浆浓度-时间曲线下从零至无穷大的面积（AUC）分别为3474.1 ± 1312.3、8156.5 ± 1782.7和25,666.8 ± 9401.1ng·h/mL；清除率CL/F分别为3.2 ± 0.9、3.8 ± 0.7和2.7 ± 1.3L/h；10mg、30mg和60mg的20(S)-人参皂苷Rg3在72小时内的尿排泄率分别为0.5 ± 0.1%、0.4 ± 0.1%和0.4 ± 0.2%。多次给药后，C 分别为457.0 ± 165.7和770.2 ± 275.4ng/mL；首次和末次20(S)-人参皂苷Rg3给药后的AUC分别为10,530.0 ± 4073.9和16,871.3 ± 6939.3ng·h/mL；波动百分比为183.0 ± 46.3%。稳态时蓄积比为1.7 ± 0.6。
20(S)-人参皂苷Rg总体耐受性良好。在这些研究中，20(S)-人参皂苷Rg3呈现出适合每两天给药一次的药代动力学特征。
