FDC formulations have also been associated with reduced T2DM-related and monthly all-cause costs as compared to respective co-administered therapies [ 26 ]. Ertugliflozin, a selective SGLT2 inhibitor, at doses of 5 mg or 15 mg QD has been shown to produce statistically significant and clinically relevant reductions in A1C, body weight, and blood pressure [ 7 , 8 , 9 , 10 , 11 ].
Several phase I studies have been conducted to assess the clinical pharmacology of ertugliflozin in healthy volunteers and in patients with T2DM. PK of ertugliflozin was predictable and similar across different study populations i. In addition, based on a population PK analysis of ertugliflozin, age did not have a clinically meaningful effect on ertugliflozin PK [ 13 ].
As per the dose vs. A1C response analysis of ertugliflozin, no dosage adjustment is recommended on the basis of age. Also, no clinically meaningful effect on the PK of ertugliflozin was observed when administered with food, and the dose-response relationship for UGE was similar under fasted and fed conditions [ 14 , 16 ].
One of the primary objectives of the present study was to demonstrate the equivalence of steady-state ertugliflozin exposure AUC 24 on day 6 of treatment at total daily dosing of 5 mg and 15 mg when administered QD vs. BID in healthy subjects 5 mg QD and 2. In a previous phase I study, ertugliflozin PK and UGE were assessed after single day dosing of 2 mg and 4 mg administered as a single dose given at breakfast and split into two doses given at breakfast and lunch in patients with T2DM.
Plasma samples for PK evaluation and urine samples for UGE were collected up to 24 hours after administration of the morning dose. At each dose level, total ertugliflozin plasma exposure observed with single and split doses was similar, as was the UGE In addition, the dose-response relationship for steady-state UGE was explored for patients with T2DM and healthy volunteers [ 27 ].
The results suggest that the dose-response relationship for steady-state UGE between patients with T2DM and healthy subjects are similar, except that dose to half-maximal response ED 50 in healthy subjects is significantly higher than that in patients with T2DM. Because of the higher ED 50 for ertugliflozin in healthy subjects, there is higher sensitivity to test similarity of UGE in healthy subjects than in patients with T2DM, as the UGE response in healthy subjects at the doses evaluated in the current study is further removed from the maximal response.
Therefore, the current study was designed in healthy subjects to evaluate the similarity of steady-state UGE 24 when ertugliflozin is dosed as QD or BID at the same total daily dose. Taken together, the findings of this study indicate that there are no meaningful differences in the PK or PD properties of ertugliflozin when administered either as BID or QD at total daily doses of 5 mg and 15 mg. In addition, both dosing regimens were well tolerated in healthy subjects. Pfizer will also consider requests for the protocol, data dictionary, and statistical analysis plan.
Data may be requested from Pfizer trials 24 months after study completion. The de-identified participant data will be made available to researchers whose proposals meet the research criteria and other conditions, and for which an exception does not apply, via a secure portal. To gain access, data requestors must enter into a data access agreement with Pfizer.
DC was an employee of MSD at the time of study conduct. National Center for Biotechnology Information , U. Int J Clin Pharmacol Ther. Published online Feb Vikas Kumar Dawra 1 Pfizer Inc. Yali Liang 1 Pfizer Inc. Haihong Shi 1 Pfizer Inc. Almasa Bass 2 Pfizer Inc. Anne Hickman 1 Pfizer Inc. Steven G.
Terra 3 Pfizer Inc. Vaishali Sahasrabudhe 1 Pfizer Inc. Author information Article notes Copyright and License information Disclaimer. Received Jul 19; Accepted Nov This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
This article has been cited by other articles in PMC. Abstract Objective: Ertugliflozin is approved in the US and European Union as a stand-alone product for adults with type 2 diabetes mellitus as once daily QD dosing. Keywords: ertugliflozin, metformin, type 2 diabetes mellitus, pharmacokinetics, pharmacodynamics. Introduction The global prevalence of type 2 diabetes mellitus T2DM is increasing and is projected to reach more than million people by ; this is largely due to the aging population and rising obesity rates [ 1 ].
Materials and methods Study objectives The primary objectives of this phase I, open-label, two-cohort, two-period, crossover study were to demonstrate the equivalence of ertugliflozin exposure AUC 24 on day 6 steady state and the similarity of UGE 24 at total daily doses of 5 mg or 15 mg when administered QD vs. Participants Healthy male and female subjects aged 18 — 55 years with body mass index Study design and treatment The study was conducted in compliance with the ethical principles of the Declaration of Helsinki and the all International Conference on Harmonisation Good Clinical Practice guidelines.
Assessments Pharmacokinetics and pharmacodynamics For each period, blood samples for PK analysis were collected for QD dosing as follows: on days 4, 5, and 6 before administration of the morning dose, and at 0. Safety All subjects who received at least 1 dose of study medication were included in the safety analysis.
Results Subject demographics 70 subjects were enrolled: 20 in cohort A 2. Table 1. Baseline characteristics. Open in a separate window. Figure 1. Median plasma ertugliflozin concentration-time profiles on day 6 after multiple QD or BID oral doses. A: Ertugliflozin 2. B: Ertugliflozin 7. Table 2. Descriptive summary of plasma ertugliflozin PK parameter values on day 6.
PK parameter summary statistics by treatment Total daily dose 5 mg Total daily dose 15 mg Ertugliflozin 2. Table 3. Parameter unit Comparison test vs. Figure 2. Table 4. Descriptive summary of UGE24 and inhibition of glucose reabsorption. Parameter units Total daily dose 5 mg Total daily dose 15 mg Ertugliflozin 2.
Safety No deaths, or serious or severe AEs occurred. Supplemental material Supplemental Table 1. Subject disposition. Click here to view. References 1. International Diabetes Federation.
IDF Diabetes Atlas, 8th edn. Brussels, Belgium: International Diabetes Federation; Centers for Disease Control and Prevention.
National Diabetes Statistics Report, Estimates of diabetes and its burden in the United States. Drug Metab Dispos. Steglatro TM ertugliflozin prescribing information. Pract Diabetes Int.
Diabetes Obes Metab. Diabetes Ther. Clin Transl Sci. J Clin Pharmacol. Pharmacogenet Genomics. Goodarzi MO Bryer-Ash M Metformin revisited: re-evaluation of its properties and role in the pharmacopoeia of modern antidiabetic agents.
Segluromet TM ertugliflozin and metformin hydrochloride prescribing information. Guidance for industry: statistical approaches to establishing bioequivalence.
Ann Intern Med. The pharmacist will translate them for the medication label. In this case, the instructions will read: "Take one tablet by mouth four times a day, after meals, and at bedtime. The abbreviations may be written in capital letters or small letters, and may or may not include periods. Some common Latin prescription abbreviations include:. The Latin terms are still in use, but some healthcare providers are retiring them. It is becoming more common for healthcare providers to write prescription instructions in plain language.
Readable prescriptions can help prevent medication errors. That is why many medical professionals think written instructions should be used instead of hard-to-read abbreviations.
For example, the abbreviation qd, which means "daily," could be mistaken for qid, which means "four times a day.
E-prescribing, or electronic prescribing, can also help prevent medication errors. Instructions sent directly to the pharmacy electronically are less prone to human error. If your healthcare provider uses electronic prescribing, you may never see the abbreviations. E-prescribing improves patient safety in a number of ways:. Healthcare providers sometimes use Latin abbreviations on prescriptions. Understanding these abbreviations can help you avoid a medication error.
Some healthcare providers are moving away from Latin abbreviations and using plain language instead. Written instructions can help prevent medication errors. Electronic prescriptions can also reduce the chance of a mistake. If you receive a written prescription, make sure you understand the directions.
If the directions are unclear or confusing, ask your healthcare provider or pharmacist to explain. Do not take your medication unless you understand the instructions.
Take no chances. If your medication is prescribed electronically, you may not see the instructions until they appear on the label. At that point, it is important to consult your pharmacist if you have questions. It is always a good idea to go over the instructions with your pharmacist. Do your part to avoid medication errors.
Sign up for our Health Tip of the Day newsletter, and receive daily tips that will help you live your healthiest life. Voice of America. Take this medicine: the story of the sign 'Rx'. Updated March 21, Pharmacy Times. A technician's guide to pharmacy abbreviations. Updated November 25, Tariq RA, Sharma S. Inappropriate medical abbreviations. In: StatPearls [Internet]. Electronic prescribing: improving the efficiency and accuracy of prescribing in the ambulatory care setting.
Perspect Health Inf Manag. Kannry J. Effect of e-prescribing systems on patient safety. Mt Sinai J Med. Cleveland Clinic. Prescription medication labels: how to read. Updated November 3, Your Privacy Rights. To change or withdraw your consent choices for VerywellHealth. At any time, you can update your settings through the "EU Privacy" link at the bottom of any page.
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