Drug Interaction Between Colchicine and Calcineurin Inhibitors in Renal Graft Recipients (COLCHINCAL)

Assistance Publique - Hôpitaux de Paris

Status and phase

Completed

Phase 1

Conditions

Renal Replacement Therapies

Treatments

Drug: tacrolimus

Drug: cyclosporine+colchicine

Study type

Interventional

Funder types

Other

Identifiers

NCT01160276

P081105

Details and patient eligibility

About

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.

Full description

Renal transplantation >= one year
eGFR (MDRD) > 30ml/min
hemoglobin >= 11g/dl
treatment with tacrolimus or cyclosporine
no previous muscular disease
no drugs interfering with P-glycoprotein or CYP3A activity or expression outcomes
colchicine AUC, Cmax, T1/2
ABCB1C3435T, CYP3A5 and SLCO1B1 genotypes

Enrollment

17 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.