Hydroxycamptothecin is an alkaloid extracted from the seeds or root bark of the deciduous plant Camptothecin, family Doveaceae. The clinical application of camptothecin is limited due to its high urinary toxicity.
Hydroxycamptothecin is an alkaloid extracted from the seeds or root bark of the deciduous plant Camptothecin, family Doveaceae. The clinical application of camptothecin is limited due to its high urinary toxicity. It is a hydroxyl derivative of camptothecin and has a similar mechanism of action to camptothecin, but is less toxic. It is an inhibitor of DNA synthesis, and experimental studies have shown that it mainly acts on the DNA synthesis phase (i.e. S-phase) and has no effect on G0-phase cells, and has a slight killing effect on G1, G2 and M-phase cells. It has inhibitory effects on a variety of animal tumors. The mechanism of action is inhibition of DNA topoisomerase I. It has no cross-resistance with commonly used antitumor drugs and has a broad antitumor spectrum in animal studies. It has a significant inhibitory effect on the synthesis of nucleic acids, especially DNA.
The clearance process of hydroxycamptothecin in blood is biphasic, with two phase organisms of 4.5 and 29 minutes, respectively. One hour after administration, the highest concentrations were maintained in the contents of gallbladder and small intestine, followed by cancer cells, and other organs such as bone marrow, stomach and lung in that order. Intravenous hydroxycamptothecin was excreted mainly from the bile and through the feces. 39% of the stomach was excreted at 24 hours, 29.6% from the feces and less than 9% in the urine, and stable levels were maintained in cancer cells over 24 hours.