The effects of ketoconazole on the pharmacokinetics of cyclosporine A in cats.
OBJECTIVE
To determine the effects of ketoconazole (KC) on the pharmacokinetics of cyclosporine A (CsA) elimination in cats.


METHODS
Research study and prospective clinical trial.


METHODS
Five healthy adult cats (pharmacokinetic studies) and 6 client-owned cats with chronic renal failure.


METHODS
Blood CsA concentrations were measured after CsA (4 mg/kg i.v.) administration with or without concurrent oral KC (10 mg/kg). Subsequently, a combined CsA-KC immunosuppressive regimen was used in cats after kidney transplantation. Blood CsA concentrations were measured using high performance liquid chromatography. CsA elimination was analyzed using a computerized pharmacokinetics program.


RESULTS
KC increased blood CsA concentrations 1.8-fold and 2.2-fold at 12 and 24 hours after CsA administration. KC significantly decreased the mean systemic CsA clearance from 2.73 mL/min/kg to 1.22 mL/min/kg resulting in an increase in the terminal phase half-life from 10.7 to 22.2 hours. The volume of distribution of steady-state of CsA was unaffected by KC. In a series of clinical feline kidney transplant patients, a once-a-day CsA-KC regimen was able to be used in most of the cats and was effective for prevention of allograft rejection in all of these cats.


CONCLUSIONS
KC is an effective adjunct treatment for immunosuppression in feline kidney transplant patients. KC suppresses CsA elimination, which reduces the need for CsA and allows once daily administration of CsA.
McAnulty
J F
JF
Department of Surgical Sciences, School of Veterinary Medicine, University Hospitals and Clinics, University of Wisconsin, Madison, USA.
Lensmeyer
G L
GL
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D019540:Area Under Curve; D002371:Cat Diseases / Q000378:metabolism / Q000601:surgery*; D002415:Cats; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006207:Half-Life; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D007654:Ketoconazole / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000601:surgery / Q000662:veterinary; D016030:Kidney Transplantation / Q000662:veterinary*; D016014:Linear Models; D011446:Prospective Studies
D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D007654:Ketoconazole