INTER-INDIVIDUAL VARIATIONS IN TACROLIMUS TREATED PATIENTS WITH RENAL TRANSPLANTS: CASE FOR PHARMACOGENTIC MONITORING
Journal Title: Innoriginal: International Journal Of Sciences - Year 2017, Vol 4, Issue 1
Abstract
Objectives: Tacrolimus is a widely used drug for renal transplant now a days. In India, it popularity has grown in recent times. One of the important feature of tacrolimus metabolism is that it has wide variation in pharmacokinetcics. Main reasons of pharmacokinetic variations are variations in intestinal and hepatic metabolism. As a result; there are wide intra and inter-patient variations. However, the incidence of these variations is not clearly known. Pharmacogentic monitoring of drugs with unpredictable pharmakinetics could be a new tool towards individualization of drug therapy. It has been known for some time that inter-individual variations contribute to drug toxicity and inferior transplant outcomes. We were interested in studying the relationship between dose and concentration in Indian patients who underwent renal transplant and to know its implications. Methods: A total of 102 patients (age range; 17-60 M:F; 87:15, mean age=29.68±20) were prescribed tacrolimus and their blood levels were analyzed to know variations in their blood levels. Oral tacrolimus therapy was initiated at a dose between 0.1 and 0.15 mg/kg/day. For monitoring tacrolimus blood concentration, blood samples were collected between 7 AM and 8 AM. Estimation of tacrolimus blood levels were done using Microparticle Enzyme Immunoassay (i Max-Abbott, USA). The analytic sensitivity of the test is 1.5ng/ml. Results: A total of 102 patients had a mean age of 29.68±20 years (age range 17-65 years). Plasma levels (ng/ml) were 10.82±7.3, 10.6±5.7, 8.92±3.85, 7.89±2/9 in the 1st, 2nd, 4th and 8th weeks respectively. The respective blood levels mentioned above were obtained with mean dosages (in mg) 7.15±6.1, 7.23±8.1, 5.94±2.5, 5.82±2.7. Multivariate analysis showed no reliable relationship between dose and concentration. Conclusions: Dose response relationship of tacrolimus is poor and routine pharmacokinetic monitoring is needed to identify patients who have low levels of this drug.
Authors and Affiliations
VIKAS DHIKAV, SANDEEP GULERIA
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