Pharmacodynamics of cyclosporine in heart and heart-lung transplant recipients. II: Blood cyclosporine concentrations and other risk factors for lung allograft rejection.
We have attempted to quantify the optimal clinical use of cyclosporine during the first 3 months after heart-lung transplantation. We used multiple logistic regression to investigate the influence of blood cyclosporine concentrations and other potential risk factors on histologically confirmed acute lung rejection in 50 heart-lung transplant recipients. A 50% increase in cyclosporine concentration was associated with a 25% reduction in risk of rejection in the subsequent 5 days (P=0.008). Increasing oral corticosteroid dose also protected against rejection (P=0.006). Rejection was over 4 times more likely to occur during the first 20 postoperative days (P=0.002). After 20 days, an FEV1 < or = 70% of the age-, sex-, and height-adjusted expected score was associated with a 4-fold increase in risk of rejection (P=0.01). Patients who had multiple previous rejection episodes were also predisposed to further rejection (P=0.005). An investigation of threshold levels for the cyclosporine concentration-effect relationship suggested that cyclosporine concentrations above 500 microg L(-1) provide optimal protection against acute lung allograft rejection. This result provides an objectively defined therapeutic threshold for targeting early cyclosporine concentrations following heart-lung transplantation.
Best
N G
NG
MRC Biostatistics Unit, Institute of Public Health, United Kingdom.
Tan
K K
KK
Trull
A K
AK
Spiegelhalter
D J
DJ
Stewart
S
S
Wallwork
J
J
D000328:Adult; D000704:Analysis of Variance; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology; D016027:Heart Transplantation; D016041:Heart-Lung Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D016040:Lung Transplantation / Q000276:immunology; D008297:Male; D011300:Preoperative Care; D012044:Regression Analysis; D012307:Risk Factors; D013997:Time Factors
D007166:Immunosuppressive Agents; D016572:Cyclosporine