Drug-Drug Interaction Study Between Colchicine and Atorvastatin
Summary
Colchicine is a substrate for cytochrome P450 3A4 (CYP3A4). In-vitro studies have indicated that the ortho-and para-hydroxylated metabolites of atorvastatin may be CYP3A4/5 competitive and mechanism-based inhibitors (MBI). This study will evaluate the effect of multiple doses of atorvastatin 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.
Description
Colchicine is a substrate for cytochrome P450 3A4 (CYP3A4). In-vitro studies have indicated that the ortho-and para-hydroxylated metabolites of atorvastatin may be CYP3A4 /5 competitive and mechanism-based inhibitors (MBI). This study will evaluate the effect of multiple doses of atorvastatin on the pharmacokinetic profile of a single 0.6 mg dose of colchicine. Twenty-four healthy, non-smoking, non-obese, non-pregnant adult volunteers between the ages of 18 and 45 will be given one oral dose of colchicine (1 x 0.6 mg tablet) on Day 1 after an overnight fast. Blood samples will be drawn from all participants before dosing and for 24 hours post-dose at times sufficient to adequately define the pharmacokinetics of colchicine. After a 14 day washout period, starting on the morning of Day 15 and continuing through Day 27, subjects will return to the clinic for once daily administration of atorvastatin (1 x 40 mg tablet) after an overnight fast. After taking the first dose of atorvastatin on Day 15, subjects will remain in the clinic for 1 hour post-dose administration for observation. On the morning of Day 28 after an overnight fast, all study participants will receive a co-administered single oral dose of colchicine (1 x 0.6 mg tablet) and atorvastatin (1 x 40 mg tablet). Blood samples will be drawn from all participants before dosing and for twenty-four hours post-dose at times sufficient to adequately define the pharmacokinetics of colchicine in the presence of atorvastatin at steady state. 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. Seated blood pressure and pulse, respiratory rate and temperature will be measured at screening, baseline and upon study discharge. Blood pressure and pulse will also be measured pre-dose and at 1 and 2 hours post-dose on Days 1 and 28 to coincide with peak plasma concentrations of colchicine and atorvastatin. 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.
Study Design
Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
Conditions
Healthy
Intervention
Colchicine, Atorvastatin, Colchicine
Location
PRACS Institute, Ltd. - Cetero Research
Fargo
North Dakota
United States
58104
Status
Completed
Source
Mutual Pharmaceutical Company, Inc.
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00960323
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Lumicolchicines
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.
Colchicine
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).
Tubulin
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.
Colchicum
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.
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