دورية أكاديمية
Pharmacokinetic-pharmacodynamic (dipeptidyl peptidase-4 inhibition) model to support dose rationale in diabetes patients, including those with renal impairment, for once-weekly administered omarigliptin.
| العنوان: | Pharmacokinetic-pharmacodynamic (dipeptidyl peptidase-4 inhibition) model to support dose rationale in diabetes patients, including those with renal impairment, for once-weekly administered omarigliptin. |
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| المؤلفون: | Jain L; Merck & Co., Inc., Kenilworth, NJ, USA., Chain ASY; Merck & Co., Inc., Kenilworth, NJ, USA., Tatosian DA; Merck & Co., Inc., Kenilworth, NJ, USA., Hing J; Cognigen Corporation, a Simulations Plus Company, Buffalo, NY, USA., Passarell JA; Cognigen Corporation, a Simulations Plus Company, Buffalo, NY, USA., Kauh EA; Merck & Co., Inc., Kenilworth, NJ, USA., Lai E; Merck & Co., Inc., Kenilworth, NJ, USA. |
| المصدر: | British journal of clinical pharmacology [Br J Clin Pharmacol] 2019 Dec; Vol. 85 (12), pp. 2759-2771. Date of Electronic Publication: 2019 Dec 09. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 7503323 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2125 (Electronic) Linking ISSN: 03065251 NLM ISO Abbreviation: Br J Clin Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Wiley-Blackwell Original Publication: London, Macmillan Journals Ltd. |
| مواضيع طبية MeSH: | Models, Biological*, Diabetes Mellitus, Type 2/*blood , Dipeptidyl-Peptidase IV Inhibitors/*blood , Heterocyclic Compounds, 2-Ring/*blood , Hypoglycemic Agents/*blood , Kidney Failure, Chronic/*blood , Pyrans/*blood , Renal Insufficiency/*blood, Blood Glucose/analysis ; Clinical Trials as Topic ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Dipeptidyl Peptidase 4/blood ; Dipeptidyl-Peptidase IV Inhibitors/administration & dosage ; Dipeptidyl-Peptidase IV Inhibitors/therapeutic use ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Heterocyclic Compounds, 2-Ring/administration & dosage ; Heterocyclic Compounds, 2-Ring/therapeutic use ; Humans ; Hypoglycemic Agents/administration & dosage ; Hypoglycemic Agents/therapeutic use ; Kidney Failure, Chronic/complications ; Kidney Failure, Chronic/drug therapy ; Pyrans/administration & dosage ; Pyrans/therapeutic use ; Renal Insufficiency/complications ; Renal Insufficiency/drug therapy |
| مستخلص: | Aims: To characterize the population pharmacokinetics (PK) and pharmacodynamics (PD) of the once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor omarigliptin in healthy subjects and patients with type 2 diabetes mellitus, and use these models to support the dosing recommendation for patient labelling including patients with renal impairment. Methods: PK and PD were assessed from a total of 9827 omarigliptin concentrations collected from 1387 healthy subjects and patients participating in Phase 1, 2 and 3 studies examining single- or multiple-dose weekly administration of omarigliptin at doses ranging from 0.25 to 400 mg. Population PK and PD analyses were performed using nonlinear mixed effect modelling. Results: A semi-mechanistic 2-compartment model with linear unbound clearance and concentration-dependent binding of omarigliptin to the DPP-4 enzyme in both the central and peripheral compartments adequately described omarigliptin PK. Key covariates on omarigliptin PK included reduced unbound clearance with renal impairment. A direct effect sigmoid maximum inhibitory efficacy model adequately described the relationship between omarigliptin plasma concentrations and DPP-4 inhibition. These models supported the current Japan label instructions that the approved omarigliptin 25-mg once-weekly dose be halved in patients with severe renal impairment and in those with end-stage renal disease. Also, if patients missed a dose, the next dose of omarigliptin should be taken as soon as remembered up to and including the day before the next scheduled dose. No other clinically important covariates were identified. Conclusion: The models in the present analysis adequately described PK and PD characteristics of omarigliptin and supported the dosing and administration section of the omarigliptin label. (© 2019 The British Pharmacological Society.) |
| References: | Xenobiotica. 2018 Jun;48(6):584-591. (PMID: 28665228) Diabetol Metab Syndr. 2013 Oct 24;5(1):57. (PMID: 24228724) J Clin Pharmacol. 2010 Aug;50(8):873-85. (PMID: 20160157) Br J Clin Pharmacol. 2019 Dec;85(12):2759-2771. (PMID: 31454094) J Clin Pharmacol. 2016 Dec;56(12):1528-1537. (PMID: 27225334) Diabetes Care. 2015 Nov;38(11):2106-14. (PMID: 26310692) J Med Chem. 2014 Apr 24;57(8):3205-12. (PMID: 24660890) Clin Pharmacol Drug Dev. 2016 Sep;5(5):383-92. (PMID: 27627194) |
| فهرسة مساهمة: | Keywords: dipeptidyl peptidase-4 inhibitor; omarigliptin; population pharmacodynamics; population pharmacokinetics; type 2 diabetes mellitus |
| المشرفين على المادة: | 0 (2-(2,5-difluorophenyl)-5-(2-(methylsulfonyl)-2,6-dihydropyrrolo(3,4-c)pyrazol-5(4H)-yl)tetrahydro-2H-pyran-3-amine) 0 (Blood Glucose) 0 (Dipeptidyl-Peptidase IV Inhibitors) 0 (Heterocyclic Compounds, 2-Ring) 0 (Hypoglycemic Agents) 0 (Pyrans) EC 3.4.14.5 (DPP4 protein, human) EC 3.4.14.5 (Dipeptidyl Peptidase 4) |
| تواريخ الأحداث: | Date Created: 20190828 Date Completed: 20200928 Latest Revision: 20210110 |
| رمز التحديث: | 20240829 |
| مُعرف محوري في PubMed: | PMC6955405 |
| DOI: | 10.1111/bcp.14103 |
| PMID: | 31454094 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1365-2125 |
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| DOI: | 10.1111/bcp.14103 |