Tailored Immunosuppression Using CYP3A5 Metaboliser Status in Heart and Lung Transplant Cases - An Indian Study

Abstract

CYP3A5 enzyme allele status affects metabolism of Calcineurin inhibitors . There is data on influence of Polymorphism in CYP alleles on Tacrolimus levels in Caucasian and Afro - American patients, but little data available for Indian patients METHODS: We studied 93 Heart, lung and Combined Heart plus lung transplant patients from our Hospital with 6 months Followup . The age range was 12 yrs to 72 yrs (70 M, 23 F) .Pattern of expression of 2 alleles CYP3A 5 *1 and * 3 were analysed to classify the patients in Two groups - Group A Poor metabolisers (*3*3) and Group B made of intermediate metaboliser (*1*3) or Extensive metaboliser (*1*1) . The Initial tacrolimus drug dosages were Planned according to the metaboliser status ie Lower doses started for group A and Higher doses started for Group B. Out of 93 patients 37 patients (39 %) were found to be Poor metabolisers, 9 patients (9.6 %) extensive metabolisers and 47 patients (50.5 %) Intermediate metabolisers . Statistical analysis was done using One way Analysis of variance for independent variables (ANOVA) . The Average time taken to reach Optimal Tacrolimus trough levels was 8.9 days in Group A versus 14.6 days in group B (p< 0.0001), Average tacrolimus Trough levels at 1 month after Transplantation was 9.7 ng/ml in group A versus 7.8 ng/ml in group B (p=NS), Average tacrolimus dose was 1.8 mg in group A and 4.07 mg in group B at 1 month (P > 0.0001) and Incidence of renal dysfunction (upto 6 months) was 18 cases out of which 8 patients were poor metabolisers (44. 5 %) . Clinical rejection episodes were seen in 9 patients . The Incidence of CYP poor metaboliser Status in Indian Patients were Found to be Midway between Caucasians and Africans. We find that Poor metabolisers Take a Shorter time to achieve Optimal tacrolimus levels after thoracic organ transplants and Similar Trough levels seen in all Patients if the Initial Tacrolimus Dose is tailored as per the CYP3A5 status, thus reducing chances of renal dysfunction, drug related side effects and Rejection .