Population Pharmacokinetic Model for Ertugliflozin in Healthy Subjects and Patients With Type 2 Diabetes Mellitus
| العنوان: | Population Pharmacokinetic Model for Ertugliflozin in Healthy Subjects and Patients With Type 2 Diabetes Mellitus |
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| المؤلفون: | Susan Zhou, Daryl J. Fediuk, Vikas Kumar Dawra, Vaishali Sahasrabudhe, Kevin Sweeney |
| المصدر: | Clinical Pharmacology in Drug Development |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, Pharmaceutical Science, 030226 pharmacology & pharmacy, Gastroenterology, 0302 clinical medicine, population pharmacokinetics, Tissue Distribution, Pharmacology (medical), Aged, 80 and over, Volume of distribution, education.field_of_study, Clinical Trials, Phase I as Topic, diabetes, Articles, Middle Aged, 030220 oncology & carcinogenesis, Female, Glomerular Filtration Rate, Adult, medicine.medical_specialty, Adolescent, ertugliflozin, Population, Biological Availability, Renal function, Original Manuscript, sodium‐glucose cotransporter 2 inhibitor, Models, Biological, Young Adult, 03 medical and health sciences, Clinical Trials, Phase II as Topic, Asian People, Pharmacokinetics, Diabetes mellitus, Internal medicine, medicine, Humans, education, Sodium-Glucose Transporter 2 Inhibitors, Aged, Glycemic, business.industry, Type 2 Diabetes Mellitus, Bridged Bicyclo Compounds, Heterocyclic, medicine.disease, Bioavailability, Clinical Trials, Phase III as Topic, Diabetes Mellitus, Type 2, Case-Control Studies, business |
| الوصف: | Ertugliflozin is a selective sodium‐glucose cotransporter 2 inhibitor approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). A population pharmacokinetic (popPK) model was developed to characterize the pharmacokinetics (PK) of ertugliflozin and quantify the influence of intrinsic (eg, body weight, age, sex, race, estimated glomerular filtration rate [eGFR], T2DM) and extrinsic (eg, food) covariates on the PK parameters of ertugliflozin. The analysis was conducted using data from 15 clinical studies (phases 1‐3) enrolling healthy subjects and patients with T2DM, which included 13,691 PK observations from 2276 subjects and was performed using nonlinear mixed‐effects modeling. A 2‐compartment popPK model with first‐order absorption and a lag time and first‐order elimination, described the plasma concentration–time profile of ertugliflozin after single and multiple dosing in healthy subjects and in patients with T2DM. Apparent clearance increased with increasing body weight and eGFR, was slightly lower in patients with T2DM and females, and was slightly higher in Asians. Apparent central volume of distribution increased with increasing body weight and was higher in females and Asians. Administration of ertugliflozin with food decreased the absorption rate constant (ka) and relative bioavailability (F1) compared with fasted. When ertugliflozin was administered without regard to food, estimates of ka and F1 were similar to those for administration with food. The popPK model successfully characterized ertugliflozin exposure in healthy subjects and patients with T2DM. None of the covariates evaluated had a clinically relevant effect on ertugliflozin PK. |
| تدمد: | 2160-7648 2160-763X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4b0e2059b44f9e2ca99a704111ddb59e https://doi.org/10.1002/cpdd.885 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....4b0e2059b44f9e2ca99a704111ddb59e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21607648 2160763X |
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