** BIOEQUIVALENCE OF TWO MICROEMULSIVE PREPARATIONS OF CYCLOSPORINE IN RENAL TRANSPLANT RECIPIENTS WITH STABLE GRAFT FUNCTION

Sud K., Sakhuja V, Pandey R, Singh B, Kohli HS, Jha V, Gupta KL.

Departments of Nephrology and Nuclear Medicine, Postgraduate institute of Medical Education & Research, Chandigarh

A number of cheaper brands of cyclosporine A (CyA) in microemulsion form have hit the Indian market in recent years. However, there is as yet a lurking apprehension amongst transplant physicians on the bioequivalence of these generic.

Preparations: The aim of this study was to compare the bioequivalence of Panimun Bioral © Panacea Biotec, India (with the most commonly prescribed preparation Sandimmun Neoral © Novarits, Switzerland). Renal transplant recipients with stable graft function defined as <20% change in the serum creatinine value in the preceding 4 weeks and having completed at least 6 months after transplantation were studied prospectively in an unblinded, cross over study design and after conersion to Panium Bioral (1.32±0.43 mg/dl, p=0.25). Patients with acute or chronic liver disease or uncontrolled diabetes mellitus. In addition, patients having received any drug known to potentiate the nephrotoxicity of CyA or patients with planned co-administration of nay other drug known to interfere in the CyA pharmacokinetics were excluded. The CyA AUCs were estimated at weekly intervals for 2 weeks before and after the 1:1 dosage switch. For calculation of area under the curve (AUC), whole blood CyA levels while on Sandimmun Neoral and after a 1:1 dosage shift over to Panimun Bioral were taken at 0, 1, 2, 4, 6 and 18 hours after the morning dose. Whole blood CyA levels were analyzed using Cyclo-Trac SP radioimmuno assay kit © Incstar Corporation, USA). Serum creatinine was checked twice a week for 2 weeks before and after the conversion. Patients exhibiting a rise in serum creatinine >20% of baseline values were required to undergo a graft biopsy to look for evidence of rejection/CyA toxicity. Those patients with an episode of rejection of CyA toxicity and responding to dosage reduction were to be excluded from the trial. All results were expressed as mean ±2SD. Paired student's t-test was used to compare differences in means. Eleven patients, all males, with a mean age of 34.65±10.9 years and receiving CyA in a dose of 3.83±0.50 mg/kg/day were included. Various pharmacokinetic parameters evaluated are shown below:

There was no change in serum creatinine values before (1.36±0.37 mg/dl) and after conversion to Panimun Bioral (1.32 ± 0.43 mg/dl, p^0.25). There were no episodes of graft dysfunction during and 4 weeks after the conversion to Panimun Bioral. We conclude that the two microemulsive formulations are bio-equivalent and conversion to the cheaper brand 6 months after transplantation is not associated with any adverse short term graft outcomes.

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