Colchicine pharmacokinetics

Pharmacokinetics Colchicine is rapidly absorbed after oral administration peak plasma concentrations occur in 0.5 to 2 hours. High colchicine concentrations are found in the kidney, liver, and spleen. It is metabolized in the liver. Excretion occurs primarily by biliary and renal routes. 

A third focus has been directed toward incorporation of conventional PET radionuclides nC or 18F into existing substrates or inhibitors known to interact with Pgp [113-115]. This strategy has been employed to produce various PET agents, including 1 -colchicine, 11C-verapamil, nC-daunomycin, and uC/18F-paclitaxel[115-123]. While promising data have been generated, some of these PET agents suffer from modest radiochemical yields and others from complex pharmacokinetics in vivo mediated, at least in part, by rapid metabolism of the radiolabeled compounds. 

Pharmacokinetics Colchicine is administered orally, followed by rapid absorption from the Gl tract. It is also available combined with probenecid (see below). Colchicine is recycled in the bile and is excreted unchanged in the feces or urine. 

Example Colchicine Route PO, IV Pregnancy Pharmacokinetic Absorbed... 

Desrayaud S, Guntz P, Scherrmann JM, Lemaire M. 1997. Effect of the P-glycoprotein inhibitor, SDZ PSC 833, on the blood and brain pharmacokinetics of colchicine. Life Sci. 61 153-63... 

Focused use of microarrays to generate large gene expression data sets relevant to transporters has been rare. To date these microarrays have been limited in the number of transporters present on them [8]. They have been used in an attempt to correlate pharmacokinetic properties with gene expression, for example, for valacyclovir [79], as well as to understand the transporter expression profile in different tissues or cell lines upon dietary component or xenobiotic treatment [1]. The lack of transporters on many commercially available microarrays has prompted some groups to produce arrays with a heavier emphasis on transporters. These arrays have, for example, then been used to demonstrate the upregulation of ABC transporters and dowmegulation of GST-Pi in cell lines resistant to colchicines or... 

The recently developed oxadiazoline A-105972 (5i) displayed reasonable cytotoxic activity towards a panel of human cancer cell lines in vitro [38], but its utility in vivo was limited by a short half-life. Further efforts led to the identification of the indolyloxozoline A-259745 (5k) [38] that demonstrated a better pharmacokinetic profile and three times increased survival of tumour bearing nude mice upon oral dosing. The mechanism of tubulin interference and the enantioselective synthesis of A-289099 (5k, S-enantiomer) have been investigated, confirming the competition with colchicine [39]. After the preclinical development no further investigation has been reported. 

---