Pharmacokinetics, tissue distribution and excretion of gambogic acid in rats.
The plasma pharmacokinetics, excretion, and tissue distribution of gambogic acid (GA), a novel anti-tumor drug, were investigated after intravenous (i.v.) bolus administration in rats. Plasma profiles were obtained after i.v. administration of GA at the doses of 1, 2 and 4 mg/kg. The elimination half-life (tl/2) values for GA were estimated to be 14.9, 15.7 and 16.1 min, while the mean area under concentration-time curve (AUC(t)) values were 54.2, 96.1 and 182.4 microg min/ml, respectively. GA was mainly excreted into the bile (36.5% over 16 h). The cumulative sum of fecal excretion within 48 h was 1.26% of the i.v. administered dose. No GA was detected in the urine after i.v. administration. GA had a limited tissue distribution, with the highest concentrations being found in the liver. GA reached its maximal concentration in all tissues at 5 min post-dose. In conclusion, the present observations indicated that GA was rapidly eliminated from the blood and transferred to the tissues. Moreover, the majority of GA appeared to be excreted into the bile within 16 h of i.v. administration.
Hao
Kun
K
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, People's Republic of China.
Liu
Xiao-Quan
XQ
Wang
Guang-Ji
GJ
Zhao
Xiao-Ping
XP
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001646:Bile / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000737:chemistry; D005260:Female; D029760:Garcinia / Q000737:chemistry; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D010936:Plant Extracts; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D044004:Xanthones / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D044004:Xanthones; C052659:gambogic acid
Acta Pharmacol Sin. 2004 Jun;25(6):769-74
15169630