Assessment of the bioequivalence of a generic cyclosporine A by a randomized controlled trial in stable renal recipients

The aim of this study was to determine the bioequivalence of Cysporin, a generic cyclosporine A, compared with Neoral in stable renal transplant recipients. Study design consisted of an open label, two-way crossover, randomized controlled trial of Cysporin versus Neoral in stable renal transplant re...

Full description

Saved in:

Bibliographic Details
Published in:	Transplantation Vol. 81; no. 5; pp. 711 - 717
Main Authors:	HIBBERD, Adrian D, TREVILLIAN, Paul R, ROGER, Simon D, WLODARCZYK, John H, STEIN, Ann M, BOHRINGER, Elizabeth G, MILSON-HAWKE, Sally M
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD Lippincott 15-03-2006
Subjects:	Adult Biological and medical sciences Biological Availability Cyclosporine - blood Cyclosporine - pharmacokinetics Drugs, Generic - pharmacokinetics Female Fundamental and applied biological sciences. Psychology Fundamental immunology Humans Immunosuppressive Agents - pharmacokinetics Kidney Transplantation Male Medical sciences Middle Aged Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Therapeutic Equivalency Tissue, organ and graft immunology Bioequivalence Generic drug Transplantation Kidney Randomization Treatment Urinary system Surgery Randomised controlled trial Clinical trial Graft Ciclosporin Immunosuppressive agent
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The aim of this study was to determine the bioequivalence of Cysporin, a generic cyclosporine A, compared with Neoral in stable renal transplant recipients. Study design consisted of an open label, two-way crossover, randomized controlled trial of Cysporin versus Neoral in stable renal transplant recipients. In all, 33 patients were enrolled; 31 were randomized and 28 were evaluable. AUCs(0-12) were done on day 14 and 28; C(0) and C(2) were done on days 0, 7, 21 and 35. Dose conversion was 1:1. Outcome measures for serum cyclosporin A concentrations expressed as the mean+/-SD were AUC(0-12) (microg x hr/L), C(max) (microg/L), C(2) (microg/L), T(max) (hr) and T(1/2) (hr). Mean and 90% CI of the ratio Cysporin/Neoral of log-transformed data were calculated using a general linear model. The main pharmacokinetic features were: AUC(0-12): Cysporin 3495+/-1319, Neoral 3853+/-1378 (P<0.05); C(max): Cysporin 755+/-301, Neoral 881+/-368 (P<0.05); C(2): Cysporin 613+/-235, Neoral 672+/-255 (P>0.05); T(max): Cysporin 1.9+/-0.8, Neoral 1.4+/-0.6 (P<0.005); and T1/2: Cysporin 8.8+/-4.3, Neoral 8.7+/-6.2 (P>0.05). Estimated ratios of Cysporin/Neoral were: AUC 0.93 (90% CI 0.88-0.98; P<0.05); C(max) 0.88 (90% CI 0.80-0.97; P<0.05); and T(max) 1.32 (90% CI 1.14-1.53; P<0.005). Both the extent and rate of absorption of Cysporin are significantly less than those of Neoral. The 90% CI for the ratios of Cysporin/Neoral for AUC and C(max) lie within 0.80-1.25. Hence in this clinical context Cysporin is pharmacologically bioequivalent with Neoral. This study illustrates the importance of testing bioequivalence of generic cyclosporine A products in transplant recipients not healthy volunteers.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-News-1 ObjectType-Feature-3
ISSN:	0041-1337 1534-6080
DOI:	10.1097/01.tp.0000181198.98232.0c