A DRUG-INTERACTION STUDY BETWEEN TICLOPIDINE AND CYCLOSPORINE IN HEART-TRANSPLANT RECIPIENTS

Objectives: Previous uncontrolled studies have suggested an interactio n 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 interacti on between cyclosporin A and ticlopidine (250 mg per day) and the tole rability of this combination in heart-transplant recipients. Methods: Twenty heart-transplant recipients were randomised into either a treat ed or a placebo group. Blood samples were drawn for time-course evalua tion of cyclosporin blood levels over a period of 12 h, following the morning intake of cyclosporin and, for platelet aggregation studies, b efore and after 14 days of ticlopidine administration. Twenty four-hou r 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 p latelet aggregation. Pharmacokinetic parameters indicate that the bioa vailability of cyclosporin A was not significantly modified by ticlopi dine. However, one patient in the ticlopidine group was withdrawn beca use of a major fall in cyclosporin blood level within 3 days of treatm ent. Urinary excretion of 6-beta-hydroxycortisol was augmented after t reatment in the ticlopidine group compared with the placebo group, sug gesting that induction of drug metabolism might have occurred. Data al so show quite a large intra-individual variability in cyclosporin bioa vailability in the placebo group, suggesting that poor absorption of t he drug formulation and/or poor compliance might have contributed to t he decreased cyclosporin blood levels in the patient withdrawn from th is study and in previous uncontrolled studies. Conclusion: Cyclosporin bioavailability was not clearly modified by a half dosage of ticlopid ine in this study. We, however, recommend closely monitoring cyclospor in blood levels when prescribing ticlopidine. Further studies will be needed with new formulations of cyclosporin or when using the full dos age of ticlopidine.