Population pharmacokinetics of ospemifene and safety evaluation of pharmacokinetic alterations caused by intrinsic and extrinsic factors was written by Kubota, Ryuji;Matsumoto, Sayaka;Wajima, Toshihiro. And the article was included in International Journal of Clinical Pharmacology and Therapeutics in 2017.HPLC of Formula: 128607-22-7 This article mentions the following:
Purpose: To develop a population pharmacokinetic (PPK) model to assess factors influencing ospemifene pharmacokinetics and to assess safety for pharmacokinetic alteration observed in drug development. Method: A PPK model was constructed using pooled ospemifene concentrations Covariates considered before start of the anal. were: age, race, body weight, BMI, albumin, alanine amino-transferase, bilirubin, and creatinine clearance. The expected distribution of ospemifene concentration was derived for the 4 cases in phase-1 studies that increased ospemifene exposure: administration to severe renal impairment subjects (case 1), administration to moderate hepatic impairment subjects (case 2), coadministration with ketoconazole (case 3), or coadministration with fluconazole (case 4). Safety information in a long-term safety trial was used to assess the potential changes in risk of adverse events with ospemifene-exposure increase. Results: The PPK parameter estimates were 9.16 L/h for CL/F, 34.3 L for V2/F, 16.4 L/h for Q/F, 250 L for V3/F, and 0.522 h-1 for ka, based on the final model. Distributions of estimated AUC in a phase-3 study largely covered the expected distribution for case 1, case 2, or case 3, but did not overlap the expected distribution for case 4. The incidences of adverse events were not associated with ospemifene exposure in the long-term safety study. Conclusions: We developed an ospemifene PPK model and identified no relevant covariate in the PPK anal. The drug appears safe to use in renal impairment, moderate hepatic impairment, and when coadministered with ketoconazole. Ospemifene should not be administered with fluconazole. In the experiment, the researchers used many compounds, for example, (Z)-2-(4-(4-Chloro-1,2-diphenylbut-1-en-1-yl)phenoxy)ethan-1-ol (cas: 128607-22-7HPLC of Formula: 128607-22-7).
(Z)-2-(4-(4-Chloro-1,2-diphenylbut-1-en-1-yl)phenoxy)ethan-1-ol (cas: 128607-22-7) belongs to alcohols. A strong base can deprotonate an alcohol to yield an alkoxide ion (R―O−). For example, sodamide (NaNH2), a very strong base, abstracts the hydrogen atom of an alcohol. Secondary alcohols are easily oxidized without breaking carbon-carbon bonds only as far as the ketone stage. No further oxidation is seen except under very stringent conditions.HPLC of Formula: 128607-22-7
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts