Pharmacokinetics of sirolimus in heart transplant recipients with chronic renal impairment

Transplantation Proceedings
E D MoloneyJ J Egan

Abstract

A common clinical problem following organ transplantation is the development of renal failure due to calcineurin inhibitors. Sirolimus offers the potential of providing appropriate immunosuppression without nephrotoxicity. This study evaluates the impact of sirolimus monotherapy on renal function in patients late following heart transplantation and correlates trough sirolimus levels with area-under-the-concentration time curve measurements. Six male patients with renal impairment late following heart transplantation (mean 8 years) were offered sirolimus therapy. Calcineurin inhibition was discontinued in all patients on commencing sirolimus. Patients started on sirolimus 2 to 5 mg/d orally. Venous blood samples for pharmacokinetic studies and repeat creatinine clearance were performed before and 6 weeks after commencement of sirolimus in all subjects. Sirolimus trough levels accurately reflected sirolimus area-under-the-concentration time curve measurements. There was no change in renal function. Mean creatinine clearance prior to commencing sirolimus was 26.7 (12.2) mL/min and the post-sirolimus creatinine clearance performed 6 weeks later was 23.4 (11.7) mL/min (P = .64). Trough levels of sirolimus correlate with drug exposur...Continue Reading

References

Jan 1, 1992·Nephron·M H GaultC Wesolowski
Dec 1, 1995·Therapeutic Drug Monitoring·S N Sehgal
Oct 13, 1998·Renal Failure·W M Bennett
May 2, 2002·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Gregory I SnellTrevor J Williams

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Citations

Jun 5, 2007·Heart Failure Clinics·Howard J Eisen
Aug 21, 2012·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·J A Kobashigawa
Feb 8, 2007·Current Opinion in Cardiology·Finn Gustafsson, Heather J Ross

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