90706
document
A drug interaction study between ticlopidine and cyclosporin in heart transplant recipients . OBJECTIVES Previous uncontrolled studies have suggested an interaction between ticlopidine , a major antiplatelet agent , and cyclosporin in heart- and kidney-transplant recipients . The aims of this study were to examine in a randomised , double-blind fashion , the possible interaction between cyclosporin A and ticlopidine ( 250 mg per day ) and the tolerability of this combination in heart-transplant recipients . METHODS Twenty heart-transplant recipients were randomised into either a treated or a placebo group . Blood samples were drawn for time-course evaluation of cyclosporin blood levels over a period of 12 h , following the morning intake of cyclosporin and , for platelet aggregation studies , before and after 14 days of ticlopidine administration . Twenty four-hour urine samples were collected for 6-beta-hydroxycortisol measurements , before and after 14 days of ticlopidine . RESULTS Although given at half the recommended daily dosage , ticlopidine significantly reduced platelet aggregation . Pharmacokinetic parameters indicate that the bioavailability of cyclosporin A was not significantly modified by ticlopidine . However , one patient in the ticlopidine group was withdrawn because of a major fall in cyclosporin blood level within 3 days of treatment . Urinary excretion of 6-beta-hydroxycortisol was augmented after treatment in the ticlopidine group compared with the placebo group , suggesting that induction of drug metabolism might have occurred . Data also show quite a large intra-individual variability in cyclosporin bioavailability in the placebo group , suggesting that poor absorption of the drug formulation and/or poor compliance might have contributed to the decreased cyclosporin blood levels in the patient withdrawn from this study and in previous uncontrolled studies . CONCLUSION Cyclosporin bioavailability was not clearly modified by a half dosage of ticlopidine in this study . We , however , recommend closely monitoring cyclosporin blood levels when prescribing ticlopidine . Further studies will be needed with new formulations of cyclosporin or when using the full dosage of ticlopidine .
90707
Intervention_Pharmacological
ticlopidine
90708
Intervention_Pharmacological
cyclosporin
90709
Intervention_Pharmacological
ticlopidine
90710
Intervention_Pharmacological
cyclosporin
90711
Intervention_Pharmacological
cyclosporin A and ticlopidine
90712
Intervention_Pharmacological
placebo
90713
Intervention_Pharmacological
cyclosporin
90714
Intervention_Pharmacological
ticlopidine
90715
Intervention_Pharmacological
cyclosporin A
90716
Intervention_Pharmacological
ticlopidine
90717
Intervention_Pharmacological
ticlopidine
90718
Intervention_Pharmacological
placebo
90719
Intervention_Pharmacological
cyclosporin
90720
Intervention_Pharmacological
placebo
90721
Intervention_Pharmacological
cyclosporin
90722
Intervention_Pharmacological
ticlopidine
90723
Intervention_Pharmacological
ticlopidine
90724
Intervention_Pharmacological
cyclosporin
90725
Intervention_Pharmacological
ticlopidine
90726
Outcome_Physical
platelet aggregation .
90727
Outcome_Other
bioavailability of cyclosporin A
90728
Outcome_Other
fall in cyclosporin blood level
90729
Outcome_Physical
Urinary excretion of 6-beta-hydroxycortisol
90730
Outcome_Other
cyclosporin bioavailability
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Outcome_Physical
cyclosporin blood levels
90732
Participant_Condition
heart transplant recipients .
90733
Participant_Sample-size
Twenty