12 research outputs found
A Computation in a Cellular Automaton Collider Rule 110
A cellular automaton collider is a finite state machine build of rings of
one-dimensional cellular automata. We show how a computation can be performed
on the collider by exploiting interactions between gliders (particles,
localisations). The constructions proposed are based on universality of
elementary cellular automaton rule 110, cyclic tag systems, supercolliders, and
computing on rings.Comment: 39 pages, 32 figures, 3 table
Physiologically Based Pharmacokinetic Modeling to Predict DrugâDrug Interactions with Efavirenz Involving Simultaneous Inducing and Inhibitory Effects on Cytochromes
Generation time of zebrafish (Danio rerio) and medakas (Oryzias latipes) housed in the same aquaculture facility
Growth of rare minnows (Gobiocypris rarus) fed different amounts of dietary protein and lipids
Physiologically Based Modelling of Darunavir/Ritonavir Pharmacokinetics During Pregnancy
Anti-apoptotic effects of IGF-I on mortality and dysmorphogenesis in tbx5-deficient zebrafish embryos
Renal Drug Transporters and Drug Interactions.
Transporters in proximal renal tubules contribute to the disposition of numerous drugs. Furthermore, the molecular mechanisms of tubular secretion have been progressively elucidated during the past decades. Organic anions tend to be secreted by the transport proteins OAT1, OAT3 and OATP4C1 on the basolateral side of tubular cells, and multidrug resistance protein (MRP)Â 2, MRP4, OATP1A2 and breast cancer resistance protein (BCRP) on the apical side. Organic cations are secreted by organic cation transporter (OCT)Â 2 on the basolateral side, and multidrug and toxic compound extrusion (MATE) proteins MATE1, MATE2/2-K, P-glycoprotein, organic cation and carnitine transporter (OCTN)Â 1 and OCTN2 on the apical side. Significant drug-drug interactions (DDIs) may affect any of these transporters, altering the clearance and, consequently, the efficacy and/or toxicity of substrate drugs. Interactions at the level of basolateral transporters typically decrease the clearance of the victim drug, causing higher systemic exposure. Interactions at the apical level can also lower drug clearance, but may be associated with higher renal toxicity, due to intracellular accumulation. Whereas the importance of glomerular filtration in drug disposition is largely appreciated among clinicians, DDIs involving renal transporters are less well recognized. This review summarizes current knowledge on the roles, quantitative importance and clinical relevance of these transporters in drug therapy. It proposes an approach based on substrate-inhibitor associations for predicting potential tubular-based DDIs and preventing their adverse consequences. We provide a comprehensive list of known drug interactions with renally-expressed transporters. While many of these interactions have limited clinical consequences, some involving high-risk drugs (e.g. methotrexate) definitely deserve the attention of prescribers