Isoniazid does not affect bioavailability of cyclosporine in renal transplant recipients.
Transplant recipients are predisposed to develop opportunistic infections such as tuberculosis, and isoniazid (INH) is used in most antitubercular therapeutic and prophylactic protocols. Cyclosporine (CyA) bioavailability increases with the concomitant use of drugs that inhibit hepatic cytochrome P-450 enzymes. There are conflicting reports on a possible interaction between the two drugs. Seven renal transplant recipients on CyA (Sandimmun Neoral) with slow acetylation status and also requiring concomitant INH prophylaxis (300 mg/day) against tuberculosis were studied. There were no significant 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 between INH levels and changes in CyA pharmacokinetic parameters before and after administration of INH. Even after all post-INH pharmacokinetic parameters were adjusted for INH levels, the differences in the above pre- and post-INH parameters did not reach statistical significance. Renal function during the study period remained constant and there were no episodes of CyA toxicity or acute rejection during and up to 4 weeks of INH treatment. We conclude that concomitant administration of INH and CyA is safe and is not associated with any appreciable alterations in the bioavailability of CyA.
Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
K
K
Sud
T
T
Muthukumar
B
B
Singh
S K
SK
Garg
H S
HS
Kohli
V
V
Jha
K L
KL
Gupta
V
V
Sakhuja
D000107:Acetylation / Q000187:drug effects; D000123:Acetyltransferases / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001682:Biological Availability; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D007538:Isoniazid / Q000494:pharmacology*; D016030:Kidney Transplantation / Q000502:physiology*; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D014376:Tuberculosis / Q000188:drug therapy
D000995:Antitubercular Agents; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000123:Acetyltransferases; D007538:Isoniazid