TY - JOUR
T1 - Preliminary pharmacokinetics (PK) of COL-3, a matrix metalloproteinase (MMP) inhibitor
AU - Rudek, Michelle A.
AU - Dyer, Valerie
AU - Hamilton, J. Michael
AU - Pluda, James M.
AU - Reed, Eddie
AU - Figg, William D.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
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U2 - 10.1016/S0009-9236(99)80308-7
DO - 10.1016/S0009-9236(99)80308-7
M3 - Article
AN - SCOPUS:0005070339
SN - 0009-9236
VL - 65
SP - 195
JO - Clinical pharmacology and therapeutics
JF - Clinical pharmacology and therapeutics
IS - 2
ER -