Intracellular unbound atorvastatin concentrations in the presence of metabolism and transport was written by Kulkarni, Priyanka;Korzekwa, Kenneth;Nagar, Swati. And the article was included in Journal of Pharmacology and Experimental Therapeutics in 2016.Formula: C6H6N4 This article mentions the following:
Accurate prediction of drug target activity and rational dosing regimen design require knowledge of drug concentrations at the target. It is important to understand the impact of processes such as membrane permeability, partitioning, and active transport on intracellular drug concentrations The present study aimed to predict intracellular unbound atorvastatin concentrations and characterize the effect of enzyme-transporter interplay on these concentrations Single-pass liver perfusion studies were conducted in rats using atorvastatin (ATV, μM) alone at 4°C and at 37°C in presence of rifampin (RIF, 20 mM) and 1-aminobenzotriazole (ABT, 1 μM), sep. and in combination. The unbound intracellular ATV concentration was predicted with a five-compartment explicit membrane model using the parameterized diffusional influx clearance, active basolateral uptake clearance, andmetabolic clearance. Chem. inhibition of uptake andmetabolismat 37°C proved to be better controls relative to studies at 4°C. The predicted unbound intracellular concentration at the end of the 50-min perfusion in the +ABT, +ABT+RIF, and the ATV-only groups was 6.5 °M, 0.58 °M, and 5.14 °M, resp. The predicted total liver concentrations and amount recovered in bile were within 0.94-1.3 fold of the observed value in all groups. The fold difference in total liver concentration did not always extrapolate to the fold difference in predicted unbound concentration across groups. Together, these results support the use of compartmental modeling to predict intracellular concentrations in dynamic organ-based systems. These predictions can provide insight into the role of uptake transporters and metabolizing enzymes in determining drug tissue concentrations In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Formula: C6H6N4).
1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. Triazoles consist of a five-membered ring containing three nitrogen atoms and are biologically active, especially as antifungal, antimicrobial and enzyme inhibitors. Many triazoles have antifungal effects: the triazole antifungal drugs include fluconazole, isavuconazole, itraconazole, voriconazole, pramiconazole, ravuconazole, and posaconazole and triazole plant-protection fungicides include epoxiconazole, triadimenol, myclobutanil, propiconazole, prothioconazole, metconazole, cyproconazole, tebuconazole, flusilazole and paclobutrazol.Formula: C6H6N4
Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics