Drug Interaction Between Colchicine and Calcineurin Inhibitors in Renal Graft Recipients

• Status: Completed
• Trial end date: 2012-01-01
• Target enrollment: 0
• Participant gender: All

Summary

Ciclosporin inhibits P-glycoprotein should increase colchicine bioavailability whereas tacrolimus should not influence colchicine disposition.

This is a prospective, controlled, open labeled study performed in renal graft recipients comparing colchicine single dose (1mg) pharmacokinetics in 14 patients treated with tacrolimus and 14 patients treated with cyclosporin.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: Institut National de la Santé Et de la Recherche Médicale, France
• Treatments: Calcineurin Inhibitors; Colchicine; Cyclosporine; Cyclosporins; Tacrolimus

Criteria

Inclusion Criteria:

• Patients with renal graft since at least 1 year

• Patients treated with ciclosporin or tacrolimus

• Are at least 18 years old.

• Glomerular filtration rate above 30 ml / min calculated using the MDRD formula

• Among the 14 patients receiving ciclosporin:

• The genotype is not a criterion for inclusion

• Among the 14 patients with tacrolimus treatment:

• 7 genotype ABCB1 3435CC, 7 genotype ABCB1 3435TT

• Recent (1 month) residual concentration of tacrolimus between 5-10ng/ml

• Recent (1 month) residual concentration of ciclosporin between 100-200ng/ml

• For women : a negative pregnancy test (serum beta hCG)

• Realization of a medical examination.

• Informed consent and writing form.

Exclusion Criteria:

• Abnormal transaminases (AST and ALT above the ULN Laboratory).

• Underlying Liver Disease (steatosis, cirrhosis, chronic hepatitis, the virus of hepatitis C or B).

• Previous history of muscle disease (drug related especially the statin type).

• Leukopenia (WBC <3000/mm3).

• Hemoglobin <11g/dl.

• Patient treated by erythropoetin (whatever its hemoglobin value).

• Abnormal CPK (greater than the ULN Laboratory).

• Prior intolerance to colchicine.

• Regular intake of the following medications associated with rhabdomyolyses:

antipsychotics, cholesterol lowering agents (statins or fibrates), zidovudine, antidepressants (selective inhibitor of serotonin reuptake) and lithium.

• Patient (e) can not refrain from consuming grapefruit juice.

• Patient (e) taking a tea based on St John's wort.

• Taking drugs inducers of P-gp or CYP3A4 (rifabutin, rifampin, carbamazepine, phenytoin, phenobarbital, efavirenz, nevirapine, protease inhibitors, griseofulvin).

• Taking drugs inhibitors of P-gp or CYP3A4 (quinidine, macrolide antibiotics, azole antifungals, protease inhibitors, amiodarone, diltiazem, verapamil).

• Chronic diarrhea.

• ABCB1 Genotype 3435CT for patients in the tacrolimus group.

• Participation in another concurrent trial.

• Patient (e) exclusion period of another trial.

• Patient (e) having reached the maximum annual amount of compensation provided by law.

• No affiliation to French social security scheme or without CMU.