Isoniazid does not affect bioavailability of cyclosporine in renal transplant recipients

Transplant recipients are predisposed to develop opportunistic infections s uch as tuberculosis, and isoniazid (INH) is used in most antitubercular the rapeutic and prophylactic protocols. Cyclosporine (CyA) bioavailability inc reases with the concomitant use of drugs that inhibit hepatic cytochrome P- 450 enzymes. There are conflicting reports on a possible interaction betwee n the two drugs. Seven renal transplant recipients on CyA (Sandimmun Neoral (R)) with slow acetylation status and also requiring concomitant INH prophy laxis (300 mg/day) against tuberculosis were studied. There were no signifi cant changes in CyA pharmacokinetic parameters including CyA trough levels, total CyA exposure and CyA clearance before and 2 weeks after instituting INH prophylaxis. There was also no statistically significant correlation be tween INH levels and changes in CyA pharmacokinetic parameters before and a fter administration of INH. Even after all post-INH pharmacokinetic paramet ers were adjusted for INH levels, the differences in the above pre- and pos t-INH parameters did not reach statistical significance. Renal function dur ing the study period remained constant and there were no episodes of CyA to xicity or acute rejection during and up to 4 weeks of INH treatment. We con clude that concomitant administration of INH and CyA is safe and is not ass ociated with any appreciable alterations in the bioavailability of CyA. (C) 2000 Prous Science. All rights reserved.