ISONIAZID DOES NOT AFFECT BIOAVAILABITY OF CYCLOSPORINE IN RENAL TRANSPLANT RECIPIENTS

Abstract

627 The incidence of tuberculosis is increasing worldwide. Transplant recipients are particularly predisposed to develop tuberculosis and Isoniazid (INH) is used in most anti-tubercular therapeutic and prophylactic protocols. Cyclosporine (CyA) bioavailability increases on concomitant use of drugs that inhibit hepatic cytochrome P-450 enzymes. There are reports expressing concern regarding the use of INH in patients treated concomitantly with CyA. Seven renal transplant recipients receiving CyA (SANDIMMUN NEORAL) in a dose of 3.9-5.7 mg/kg/day and requiring concomitant INH prophylaxis (300 mg/day) against tuberculosis were studied. Acetylation status was assessed before inclusion in the study protocol and only slow acetylators were studied. Whole blood CyA levels at 0,1,2,4,6 and 8 hours of last dose were estimated by RIA on days 0 and 14 of starting INH and total CyA exposure (AUC) and CyA clearance calculated. The pharmacokinetic parameters before and after INH administration are shown in the Table:TableEven after post INH Cmin, Cmax, Tmax, AUCs and CyA clearance values were adjusted for INH levels, the differences in the above pre and post INH parameters did not reach statistical significance. There was also no statistically significant correlation between INH levels and changes in Cmin, Cmax, Tmax. AUCs and CyA clearance before and after administration of INH. There was no significant change in the serum creatinine levels before (1.49±0.49 mg/dl) and after INH administration (1.44±0.53 mg/dl, p>0.05). There were no episodes of CyA toxicity or acute rejection during and upto 4 weeks of starting INH. We conclude that concomitant administration of INH and CyA is safe and is not associated with any appreciable alterations in bioavailability of CyA.