Randomized, open-label, comparative phase IV study on the bioavailability of Ciclosporin Pro (Teva) versus Sandimmun® Optoral (Novartis) under fasting versus fed conditions in patients with stable renal transplants

BACKGROUND: The influence of pre- or postprandial administration on pharmacokinetics of cyclosporine is supposed to be less in gel-based formulations than in microemulsions. This study was designed to investigate the influence of a high-fat meal on the pharmacokinetic profile of the two cyclosporine containing formulations Ciclosporin Pro (gel-based emulsion) and Sandimmun®Optoral (microemulsion) in renal transplant recipients. METHODS: A randomized, open-label, repeated-measurement, comparative phase IV trial was conducted with two sequence groups for nutrition condition (fasting→fed, fed→fasting) and two treatment phases (Sandimmun® Optoral → Ciclosporin Pro), each covering both nutrition conditions. Primary pharmacokinetic variable of interest was the reduction of bioavailability due to high-fat food compared to fasting conditions measured by the difference D of ln-transformed bioavailability variables (AUC(SS, τ), C(ss, max), und C(ss, min)). RESULTS: A nutrition effect was found for both study medications with respect to the parameters AUC(SS, τ) and C(SS, max), but not to C(SS, min). The reduction of bioavailability caused by high-fat food was not significantly different for Sandimmun®Optoral and Ciclosporin Pro. CONCLUSIONS: An effect of high-fat breakfast prior to the morning dose on AUC(SS, τ) and C(SS, max) was found for Sandimmun® Optoral and for Ciclosporin Pro(.) Trough level monitoring did not capture ingestion-related variability. Conversion to Ciclosporin Pro seems to be safe with regard to intra-individual pharmacokinetic variability. TRIAL REGISTRATION: EudraCT No. 2009–011354-18 (29th April 2019) ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12882-019-1340-z) contains supplementary material, which is available to authorized users.