Track topics on Twitter Track topics that are important to you
Colchicine is a substrate for both cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp). Verapamil hydrochloride is a potent inhibitor of cytochrome P450 (CYP) 3A4 and P-gp. This study will evaluate the effect of multiple doses of extended-release verapamil hydrochloride (verapamil HCl ER) on the pharmacokinetic profile of a single 0.6 mg dose of colchicine. A secondary objective is to evaluate the safety and tolerability of this regimen in healthy volunteers. All study subjects will be monitored for adverse events throughout the study period.
Colchicine is a substrate for both cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp). Verapamil hydrochloride is a potent inhibitor of cytochrome P450 (CYP) 3A4 and P-gp. This study will evaluate the effect of multiple doses of extended-release verapamil hydrochloride (verapamil HCl ER) on the pharmacokinetic profile of a single 0.6 mg dose of colchicine. On study Day 1 after a fast of at least 10 hours, twenty-four healthy, non-smoking, non-obese, non-pregnant adult volunteers between the ages of 18 and 45 will be given one dose of colchicine (1 x 0.6 mg tablet). Fasting will continue for 4 hours after the dose. Blood samples will be drawn from all participants before dosing and for 24 hours post-dose on a confined basis at times sufficient to adequately define the pharmacokinetics of colchicine. Blood sampling will then continue on a non-confined basis on Days 2-5. After a 14 day washout period, on Day 15 subjects will return to the clinic for dosing of verapamil HCl ER (1 x 240 mg tablet) and a post-dose confinement period of 12 hours. Subjects will return on Days 16-19 for a morning dose of verapamil HCl ER (1 x 240 mg tablet). Verapamil HCl ER doses administered on Days 15-18 will not necessarily be in a fasted state. On the morning of Day 19 after a fast of at least 10 hours, all study participants will receive co-administered single doses of colchicine (1 x 0.6 mg) and verapamil HCl ER (1 x 240 mg). Fasting will continue for 4 hours following these doses and subjects will be confined to the clinic for dosing and for 24 hours after the dose. Blood samples will be drawn at times sufficient to adequately define the pharmacokinetics of colchicine in the presence of verapamil HCL at steady state. Blood sampling will continue on a non-confined basis on Days 20-23. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers. Subjects will be monitored throughout participation in the study for adverse reactions to the study drug and/or procedures. Vital signs (blood pressure and pulse) will be measured pre-dose and 1, 2, and 3 hours post-dose on Day 1, pre-dose and 12 hours post-dose on Day 15, and pre-dose and 1, 2 ,3 and 12 hours post-dose on Day 19 to coincide with peak plasma concentrations of both colchicine and verapamil HCl ER. All adverse events whether elicited by query, spontaneously reported, or observed by clinic staff will be evaluated by the Investigator and reported in the subject's case report form.
Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
Colchicine, Verapamil HCl ER, Colchicine
PRACS Institute, Ltd. - Cetero Research
East Grand Forks
Mutual Pharmaceutical Company, Inc.
Published on BioPortfolio: 2014-08-27T03:19:06-0400
Clarithromycin is a potent inhibitor of the activity of cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp). CYP 3A4 plays a role in the metabolism of colchicine and P-gp is responsible f...
This open label, single group, sequential dose study will compare the single dose pharmacokinetics of colchicine 0.6 mg given orally to colchicine pharmacokinetics after 10 days of a stan...
This randomized, single dose, three-way crossover study will evaluate the bioequivalence of two formulations of colchicine, the test product (colchicine 0.6mg Mutual) and a marketed combin...
Ritonavir is a potent inhibitor of CYP3A4, one of the enzymes responsible for the metabolism of colchicine. This study will evaluate the effect of multiple doses of ritonavir on the pharm...
Ketoconazole is a potent inhibitor of the cytochrome P450 (CYP) 3A4 enzyme system, one of the enzyme systems responsible for the metabolism of colchicine. This study will evaluate the eff...
Colchicine is an ancient medication that is currently approved for the treatment of gout and FMF. However, colchicine has a wide range of anti-inflammatory activities, and studies indicate that it may...
Colchicine is an anti-inflammatory agent used in the treatment of several rheumatological conditions. The use of colchicine in pregnancy is controversial. The current study aimed to systematically rev...
Antimitotic colchicine possesses low therapeutic index due to high toxicity effects in non-target cell. However, diverse colchicine analogs have been derivatized as intentions for toxicity reduction a...
Drug-induced injury (DILI) is a frequent cause of abnormal liver tests and a leading cause of liver failure in the United States. Colchicine has long been used as a systemic anti-inflammatory agent fo...
Our efforts to get therapeutically useful colchicine derivatives for the treatment of cancer have led us to synthetize and biologically evaluate twenty-seven N,N'-disubstituted ureas containing a colc...
Three, alpha, beta, and gamma isomers of ultraviolet degradation products of colchicine that lack many of the physiological actions of the parent; used as experimental control for colchicine actions.
A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (PERIODIC DISEASE).
A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from SPERM FLAGELLUM; CILIA; and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to COLCHICINE; VINCRISTINE; and VINBLASTINE.
A genus of poisonous, liliaceous plants. The roots (corms) of Colchicum autumnale, the fall crocus or meadow saffron, yield COLCHICINE, which is used as a biochemical tool and to treat gout. Other members of this genus yield saffron dye, flavoring agents, and aromatics.
A calcium channel blocker that is a class IV anti-arrhythmia agent.
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...
Obesity is the condition in which excess fat has accumulated in the body (mostly in subcutaneous tissues). clinical obesity is considered to be present when a person has a BMI of over 30 (Oxford Dictionary of Medicine). It is becoming increasing common i...
Obstetrics and gynaecology
Fertility Menopause Obstetrics & Gynaecology Osteoporosis Women's Health Obstetrics and gynaecology comprises the care of the pregnant woman, her unborn child and the management of diseases specific to women. Most consultant...