MMP inhibitors are a class of compounds which may have anti-angiogenic and antimetastatic properties. A Phase I clinical trial of COL-3, a non-antimicrobial tetracycline analogue, is being conducted at the NCI in patients with solid tumors. In vivo effects occurred between 1860 to 12000 ng/ml in preclinical models. Currently, fifteen patients are enrolled on 3 dosage levels (36, 50 and 70 mg/m2). Daily oral dosing begins after the PK test dose. Using an HPLC assay developed in our laboratory, concentrations of COL-3 were determined. To date, the PK of 50 mg has been characterized. Single Dose PK (N=4): Dose Cmax Tmax ka Tl/2 Cl (mg) (ng/ml) (h) (l/h) (h) (L/h) 50 1875.6 9.07± 3.505± 85.83± 0.236± ±261.6 8.80 5.468 16.80 0.059 *mean±SD Multiple dose PK (N=5) is consistent with single dose PK with a half-life of 67.99±22.61h. Cmax ss is 6672±3266 ng/ml. These data suggest COL-3 is well absorbed and has a longer half-life than other tetracycline analogues.
ASJC Scopus subject areas
- Pharmacology (medical)