Veterinary surgery : VS · 1999
The effects of ketoconazole on the pharmacokinetics of cyclosporine A in cats.
Клиническое исследованиеСтатьяРандомизированное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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McAnulty J F, Lensmeyer G L
Аннотация
OBJECTIVE: To determine the effects of ketoconazole (KC) on the pharmacokinetics of cyclosporine A (CsA) elimination in cats.
STUDY DESIGN: Research study and prospective clinical trial.
ANIMALS: 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.
CONCLUSION AND CLINICAL RELEVANCE: 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.
STUDY DESIGN: Research study and prospective clinical trial.
ANIMALS: 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.
CONCLUSION AND CLINICAL RELEVANCE: 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.