Pharmacokinetics of sirolimus in heart transplant recipients with chronic renal impairment.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
Trough levels of sirolimus correlate with drug exposure and may be used to monitor sirolimus therapy. No improvement in renal function following calcineurin inhibitor withdrawal occurred in this cohort.
Moloney
E D
ED
National Heart and Lung Transplant Programme, Mater Misericordiae University Hospital, University College Dublin, Dublin, Ireland.
O'Mahony
U
U
Kirwan
M
M
McCarthy
J
J
Hurley
J
J
Wood
A E
AE
Egan
J J
JJ
D000368:Aged; D019540:Area Under Curve; D002908:Chronic Disease; D002940:Circadian Rhythm; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D007674:Kidney Diseases / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000276:immunology*; D020123:Sirolimus / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013997:Time Factors
D007166:Immunosuppressive Agents; D020123:Sirolimus