Interaction between probucol and cyclosporine in renal transplant patients.
OBJECTIVE
To investigate a possible interaction between probucol and cyclosporine during coadministration.


METHODS
Before/after trial of 15 weeks' duration.


METHODS
Clinical pharmacokinetics laboratory of a teritiary care center.


METHODS
Ten renal transplant patients who were immunosuppressed with cyclosporine therapy for at least six months and who had been receiving probucol for more than eight weeks.


METHODS
Patients continued to receive probucol during the first five weeks of the trial (phase A). Probucol then was discontinued until the end of the trial (phase B). Blood samples from each patient were collected at weekly intervals during phase A and again during the last five weeks of phase B. Samples were assayed by fluorescence polarization immunoassay (TDx) to determine trough concentrations of the cyclosporine parent compound in whole blood, and of cyclosporine and metabolites in whole blood and in plasma. Comparison of the data was performed using a paired t-test.


RESULTS
An increase in trough concentrations of cyclosporine was observed in phase B (without probucol) with respect to phase A (with probucol). These differences were statistically significant for the cyclosporine parent compound in whole blood (p = 0.02), and for cyclosporine and metabolites in whole blood (p = 0.02) and in plasma (p = 0.001).


CONCLUSIONS
When cyclosporine and probucol are coadministered in transplant patients, a close monitoring of cyclosporine concentrations is advised because probucol can induce a decrease in trough concentrations of cyclosporine.
Gallego
C
C
Department of Pharmacy, Hospital La Fe, Valencia, Spain.
Sánchez
P
P
Planells
C
C
Sánchez
S
S
Monte
E
E
Romá
E
E
Sánchez
J
J
Pallardó
L M
LM
D000328:Adult; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011341:Probucol / Q000008:administration & dosage / Q000009:adverse effects*
D016572:Cyclosporine; D011341:Probucol