PurposeTacrolimus (Tac) and cyclosporine (CsA) are mainly metabolized by CYP3A4 and CYP3A5. Several studies have demonstrated an association between the CYP3A5 genotype and Tac dose requirements. Recently, CYP3A4, PPARA, and POR gene variants have been shown to influence CYP3A metabolism. The present study investigated potential associations between CYP3A5*3, CYP3A4*22, PPARA c.209-1003G>A and c.208 + 3819A>G, and POR*28 alleles and dose-adjusted concentrations (C/D) of Tac and CsA in 177 renal transplant patients early post-transplant.MethodsAll patients (n = 177) were genotyped for CYP3A4*22, CYP3A5*3, POR*28, PPARA c.209-1003G>A, and PPARA c.208 + 3819A>G using real-time polymerase chain reaction (PCR) and melting curve analysis with allele-specific hybridization probes or PCR restriction fragment length polymorphisms (RFLP) methods. Drug concentrations and administered doses were retrospectively collected from patient charts at Oslo University Hospital, Rikshospitalet, Norway. One steady-state concentration was collected for each patient.ResultsWe confirmed a significant impact of the CYP3A5*3 allele on Tac exposure. Patients with POR*28 and PPARA variant alleles demonstrated 15 % lower (P = 0.04) and 19 % higher (P = 0.01) Tac C0/D respectively. CsA C2/D was 53 % higher among CYP3A4*22 carriers (P = 0.03).ConclusionThe results support the use of pre-transplant CYP3A5 genotyping to improve initial dosing of Tac, and suggest that Tac dosing may be further individualized by additional POR and PPARA genotyping. Furthermore, initial CsA dosing may be improved by pre-transplant CYP3A4*22 determination.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-014-1656-3) contains supplementary material, which is available to authorized users

This paper presents the characteristics of hydrodynamically focused streams to be used in Microscale Particle Image Velocimetry (micro-PIV). The investigation was done by means of Confocal Laser Scanning Microscopy (CLSM) in channels of cross sections 260 × 200 μm and 1040 × 800 μm, within the downstream velocities range from 0,1 to 2,5 cm/s. The formulation of a curvature of the sheet, its dependence on the side stream ratio and overall downstream velocity is discussed qualitatively and quantitatively. The results show that the curvature is highly dependent on the velocities of the system. Sheet characteristics such as curvature and observed sheet width variation become amplified with higher velocities. This leads to conclusion that hydrodynamic focusing is promising as a selective seeding technique for use in micro-PIV up to velocities of few cm/s. However, the fact that this is the upper velocity range in microfluidics, renders the SeS-PIV technique as a very suitable tool for complicated flows visualization.

This paper presents the characteristics of hydrodynamically focused streams to be used in Microscale Particle Image Velocimetry (micro-PIV). The investigation was done by means of Confocal Laser