Pharmacogenomic, Pharmacokinetics
Conditions
Keywords
UGT polymorphism, Pharmacokinetics, Empagliflozin
Brief summary
The aim of this works is to investigate the effect of genetic polymorphism of snps on human response to treatment with empagliflozin and its correlation with with pharmacokinetic parameters in Egyptian subjects
Detailed description
Empagliflozin is a sodium glucose co-transporter-2 (SGLT-2) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes. SGLT2 co-transporters are responsible for reabsorption of glucose from the glomerular filtrate in the kidney. The glucuretic effect resulting from SGLT2 inhibition reduces renal absorption and lowers the renal threshold for glucose, therefore resulting in increased glucose excretion. Additionally, it contributes to reduced hyperglycaemia and also assists weight loss and blood pressure reduction. ABSORPTION Following oral administration, peak plasma concentrations were reached at 1.5 hours post-dose and then declined in a biphasic manner with a rapid distribution phase and a relatively slow terminal phase. Administration following a high-fat and high-calorie meal results in a slightly lower exposure with area under the curve (AUC) decreasing by approximately 16% and Cmax decreasing by approximately 37% compared to fasted condition. METABOLISM In vitro studies suggest that empagliflozin is primarily metabolized by glucuronidation by 5'-diphospho-glucuronosyltransferases UG2B7, UGT1A3, UGT1A8, and UGT1A9. The most abundant metabolites are three glucuronide metabolites: 2-O-, 3-O-, and 6-O-glucuronide. Empagliflozin does not inhibit, inactivate, or induce CYP450 isoforms. It is a substrate for p-glycoprotein (p-gp), however in vitro studies suggest that it is unlikely to cause interactions with drugs that are p-gp substrates. After oral administration, empagliflozin was 41.2% eliminated in feces and 54.4% eliminated in urine. Terminal elimination half life was found to be 12.4 h based on population pharmacokinetic analysis.
Interventions
DRUGEmpagliflozin 10 milligram
antihyperglycemic medication
Sponsors
Ain Shams University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
open label, single-dose, one-period, design
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adult volunteers * Age between (18-45 years) * Normal BMI. * Understand the procedures and are willing to participate and gave their final written consent prior to the commencement of the study procedures. * The volunteers will be asked to provide a complete medical history, and complete a physical examination, laboratory tests \[hematology, clinical chemistry, urinalysis, serology (including hepatitis B surface antigen, anti-hepatitis C virus and antihuman immunodeficiency virus antibody).
Exclusion criteria
* Treatment with any known enzyme-inducing/inhibiting agents within 30 days prior to the start of the study and throughout the study. * Subjects who have taken any medication less than two weeks of the trials starting date. * Susceptibility to allergic reactions to study drugs. * Any prior surgery of the gastrointestinal tract that may interfere with drug absorption. * Gastrointestinal diseases. * Renal diseases. * Cardiovascular diseases. * Pancreatic disease including diabetes. * Hepatic diseases. * Hematological disease or pulmonary disease * Abnormal laboratory values. * Subjects who have donated blood or who have been involved in multiple dosing study requiring a large volume of blood (more than 500 ml) to be drawn within 6 weeks preceding the start of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic parameters | 48 hours | AUC0→∞ |
| Bioavailability parameters | 24 hours | Cmax |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary outcome | 48 hours | Tmax |
Countries
Egypt
Outcome results
None listed