The pharmacokinetics and bioequivalence of Gengraf and Neoral in stable renal transplant recipients

AbstractObjectiveGengraf capsule, an AB-rated generic cyclosporine for Neoral, has been shown to be bioequivalent in previous studies. The objective of this study was to evaluate the pharmacokinetics and bioequivalence of Gengraf and Neoral in stable Chinese renal allograft recipientsMethodsIn a prospective, open-label, two-period design study, 20 renal allograft recipients receiving stable doses of Neoral were recruited. Subjects continued their Neoral regimen during period I (days 1-14). They were then switched from Neoral on a milligram-for-milligram basis to Gengraf during period II (days 15-28). Four-hour pharmacokinetic parameters (concentration before dosing [Ctrough], maximum blood concentration [Cmax], time to maximum concentration [Tmax], and area under the blood concentration-versus-time curve [AUC0-4]) were taken on days 1, 8, 21, and 28. Biochemical parameters were also evaluated.ResultsThere was no significant difference in the pharmacokinetics of Gengraf (Ctrough, Tmax, Cmax, and AUC0-4) as compared with that of Neoral in stable renal transplant recipients. The bioequivalent capsules were interchangeable with respect to Ctrough, Cmax and AUC0-4. The 90% confidence intervals of the ratio of Ctrough, Cmax, Tmax, and AUC0-4 of Gengraf and Neoral were 0.94 to 1.21 for Ctrough, 0.97 to 1.20 for Cmax, and 0.97 to 1.20 for AUC0-4. Ctrough and C2 remained stable throughout the study without any dosage adjustments. Gengraf was well tolerated, and had a comparable safety profile as Neoral.ConclusionGengraf are bioequivalent to Neoral. Gengraf is well tolerated and interchangeable with Neoral in stable Chinese renal allograft recipients

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field