Preliminary pharmacokinetics (PK) of COL-3, a matrix metalloproteinase (MMP) inhibitor

Michelle A. Rudek; Valerie Dyer; J. Michael Hamilton; James M. Pluda; Eddie Reed; William D. Figg

doi:10.1016/S0009-9236(99)80308-7

Preliminary pharmacokinetics (PK) of COL-3, a matrix metalloproteinase (MMP) inhibitor

Michelle A. Rudek^*, Valerie Dyer, J. Michael Hamilton, James M. Pluda, Eddie Reed, William D. Figg

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

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 C_max T_max k_a T_l/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. C_{max ss} is 6672±3266 ng/ml. These data suggest COL-3 is well absorbed and has a longer half-life than other tetracycline analogues.

Original language	English
Pages (from-to)	195
Number of pages	1
Journal	Clinical Pharmacology and Therapeutics
Volume	65
Issue number	2
DOIs	https://doi.org/10.1016/S0009-9236(99)80308-7
State	Published - 1999
Externally published	Yes

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title = "Preliminary pharmacokinetics (PK) of COL-3, a matrix metalloproteinase (MMP) inhibitor",

abstract = "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.",

author = "Rudek, \{Michelle A.\} and Valerie Dyer and Hamilton, \{J. Michael\} and Pluda, \{James M.\} and Eddie Reed and Figg, \{William D.\}",

year = "1999",

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pages = "195",

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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

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AN - SCOPUS:0005070339

SN - 0009-9236

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SP - 195

JO - Clinical Pharmacology and Therapeutics

JF - Clinical Pharmacology and Therapeutics

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ER -

Preliminary pharmacokinetics (PK) of COL-3, a matrix metalloproteinase (MMP) inhibitor

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