Pharmacokinetics of a new fixed-dose combination of candesartan cilexetil, hydrochlorothiazide, and rosuvastatin in healthy adult subjects was written by Yerino, Gustavo A.;Feleder, Ethel C.;Halabe, Emilia K.;Diaz, Liliana;Sakson, Mario;Iglesias, Mariana;Haddad, Tobias;Roldan, Emilio;Mondelo, Nelida. And the article was included in International Journal of Clinical Pharmacology and Therapeutics in 2022.Safety of 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate This article mentions the following:
A fixed-dose combination (FDC) of candesartan cilexetil, hydrochlorothiazide and rosuvastatin (CC/ HCTZ/RSV) has been developed to enhance patient compliance in the primary prevention of cardiovascular diseases. To evaluate if the combination of the product components in the new FDC capsule formulation affects their resp. pharmacokinetic and in vitro dissolution patterns. Materials and methods: In vitro dissolution profiles were compared in USP-43 and in biorelevant dissolution media. In vivo comparisons were obtained in a randomized, open-label, single-dose, two-treatment, two-way crossover study in 24 healthy subjects. During each treatment period, subjects received the test formulation (FDC hard capsule containing CC/HCTZ/RSV) or the reference formulation (co-administration of a FDC CC/HCTZ tablet and a RSV tablet). Plasma samples were collected periodically over 48 h post-dose. Safety and tolerability were assessed. Dissolution profiles of all active drugs in the Test (capsule) and Reference Products (as tablets) were within the tolerance dissolution criteria of USP-43 conditions. HCTZ dissolution profiles were closely similar whereas those for RSV and CC did not match at specific pHs. In the pharmacokinetic study, the 90% confidence intervals (CIs) for the geometric least-square mean ratios of Cmax, AUC0-last, and AUC0-inf were 0.95 – 1.18, 0.95 – 1.15 and 0.95 – 1.13 (CC); 0.91 – 1.10, 0.96 – 1.08, and 0.96 – 1.09 (HCTZ) and 0.82 – 1.23, 0.81 – 1.13, and 0.82 – 1.12 (RSV), resp. All adverse events were mild. The new FDC product (Sinlip Prevent), a stable FDC hard capsule, was bioequivalent (similar pharmacokinetics) when compared to the coadministration of the components and may be considered as a suitable and simplified medication for cardiovascular disease management. In the experiment, the researchers used many compounds, for example, 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5Safety of 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate).
1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate (cas: 145040-37-5) belongs to imidazole derivatives. The solubility of imidazoles in ethers is lower than that in alcohols and decreases with increasing chain length of the ethers . In contrast, the solubility of benzimidazoles in alcohols (C3–C6) is higher than in water and generally decreases with a Many drugs contain an imidazole ring, such as certain antifungal drugs, the nitroimidazole series of antibiotics, and the sedative midazolam.Safety of 1-(((Cyclohexyloxy)carbonyl)oxy)ethyl 1-((2′-(2H-tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem