RESUMEN
Many studies have shown that the efficacy and risk of side effects of drug treatment is influenced by genetic variants. Evidence based guidelines are essential for implementing pharmacogenetic knowledge in daily clinical practice to optimize pharmacotherapy of individual patients. A literature search was performed to select committees developing guidelines with recommendations being published in English. The Dutch Pharmacogenetics Working Group (DPWG), the Clinical Pharmacogenetics Implementation Consortium (CPIC), the Canadian Pharmacogenomics Network for Drug Safety (CPNDS), and the French National Network (Réseau) of Pharmacogenetics (RNPGx) were selected. Their guidelines were compared with regard to the methodology of development, translation of genotypes to predicted phenotypes, pharmacotherapeutic recommendations and recommendations on genotyping. A detailed overview of all recommendations for gene-drug combinations is given. The committees have similar methodologies of guideline development. However, the objectives differed at the start of their projects, which have led to unique profiles and strengths of their guidelines. DPWG and CPIC have a main focus on pharmacotherapeutic recommendations for a large number of drugs in combination with a patient's genotype or predicted phenotype. DPWG, CPNDS and RNPGx also recommend on performing genetic testing in daily clinical practice, with RNPGx even describing specific clinical settings or medical conditions for which genotyping is recommended. Discordances exist, however committees also initiated harmonizing projects. The outcome of a consensus project was to rename "extensive metabolizer (EM)" to "normal metabolizer (NM)". It was decided to translate a CYP2D6 genotype with one nonfunctional allele (activity score 1.0) into the predicted phenotype of intermediate metabolizer (IM). Differences in recommendations are the result of the methodologies used, such as assessment of dose adjustments of tricyclic antidepressants. In some cases, indication or dose specific recommendations are given for example for clopidogrel, codeine, irinotecan. The following drugs have recommendations on genetic testing with the highest level: abacavir (HLA), clopidogrel (CYP2C19), fluoropyrimidines (DPYD), thiopurines (TPMT), irinotecan (UGT1A1), codeine (CYP2D6), and cisplatin (TPMT). The guidelines cover many drugs and genes, genotypes, or predicted phenotypes. Because of this and their unique features, considering the totality of guidelines are of added value. In conclusion, many evidence based pharmacogenetics guidelines with clear recommendations are available for clinical decision making by healthcare professionals, patients and other stakeholders.
RESUMEN
With the global population rising, the need for sustainable and resource-efficiently produced proteins with nutritional and health promoting qualities has become urgent. Proteins are important macronutrients and are involved in most, if not all, biological processes in the human body. This review discusses these absorption mechanisms in the small intestine. To study intestinal transport and predict bioavailability, cell lines are widely applied as screening models and often concern Caco-2, HT-29, HT-29/MTX and T84 cells. Here, we provide an overview of the presence and activities of peptide- and amino acid transporters in these cell models. Further, inter-laboratory differences are discussed as well as the culture micro-environment, both of which may influence cell culture phenotype and performance. Finally, the value of new developments in the field, including culturing cells in 3-dimensional systems under shear stress (i.e., gut-on-chips), is highlighted. In particular, their suitability in screening novel food proteins and prediction of the nutritional quality needed for inclusion in the human diet of the future is addressed.
