Quantitative estimation of intra-subject variability in bioequivalence studies of generic solid oral dosage forms by multiple regression analysis was written by Wada, Shigenori;Kagatani, Seiya;Nakagami, Hiroaki. And the article was included in Journal of Drug Delivery Science and Technology in 2021.Name: 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:
Intra-subject variability (CVintra), which determines the 90% confidence intervals and the number of subjects needed for assessment in bioequivalence studies, is generally investigated by using pilot study Results. However, conducting pilot studies greatly affects the speed and cost of drug development. In this study, we performed multiple regression anal. of the major factors that predict the extent of the CVintra of pharmacokinetic parameters by using 4 quant. variables (drug solubility, variability of the peak drug concentration [Cmax] or area under the drug plasma concentration vs. time curve [AUC], bioavailability, and elimination half-life), which were obtained from a database of the results of bioequivalence studies conducted by Nihon Generic Co., Ltd. A total of 77 studies [34 components] were included. From this anal., we confirmed that multiple regression equations can be used to estimate 3 kinds of %CVintra values with high correlation coefficients (r = 0.8971 for the Cmax of all drug types, r = 0.9739 for the AUC of renal excretion-type drugs, and r = 0.5368 for the AUC of non-renal excretion-type drugs). When the predicted equations were applied to newly planned bioequivalence studies (2 studies [2 components]) without pilot studies, it was verified that the %CVintra of the Cmax and AUC could be estimated with a predicted value of ±5. Further, both formulations were found to be bioequivalent in term of the Cmax and AUC, with 90% confidence intervals of sufficient power. 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: 145040-37-5Name: 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. Imidazole is the basic core of some natural products such as histidine, purine, histamine and DNA based structures, etc. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Imidazole based anticancer drug find applications in cancer chemotherapy. It is used as buffer component for purification of the histidine tagged recombinant proteins in immobilized metal-affinity chromatography (IMAC).Name: 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