Diabetes Mellitus, Type 2, Drug Interaction, Erectile Dysfunction With Diabetes Mellitus
Conditions
Brief summary
Patients with diabetes are three times more likely to develop erectile dysfunction (ED), and longer duration of diabetes is strongly associated with ED. The possibility of pharmacokinetic interactions may occur as the two drugs are metabolized by hepatic CYP3A4 and their co administration may affect their plasma concentrations. the aim of work is to investigate the effect of sildenafil a CYP3A4 substrate and inhibitor on the pharmacokinetics and safety of Saxagliptin, a CYP3A4 substrate Subjects and Methods: Eighteen healthy volunteers will be recruited in Sequential, single center study to determine pharmacokinetic parameters of Saxagliptin, and sildenafil,(AUC0→∞), (AUC0→t); Cmax; tmax; t½, k; ka) will be measured using validated LC-MS/MS method. Therapeutic doses will be given to volunteers as follows: Sildenafil 50 mg single dose on day 1, then washout period from day 2 till day 8. Saxagliptin 5 mg once/day will be given from day 9 till day 12, then on day 13 the two drugs will be co-administered. Blood samples (5ml) for pharmacokinetic analysis will be collected on days 1 and 13 for Sildenafil as well as on days 12 and 13 for Saxagliptin.
Interventions
DRUGSaxagliptin 5mg
Saxagliptin 5mg oral tablet
DRUGSildenafil 50 mg
Sildenafil 50 mg Oral Tablet
Sponsors
Ain Shams University
Study design
Intervention model
SEQUENTIAL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Intervention model description
Eighteen healthy volunteers will be recruited in Sequential, single center study to determine pharmacokinetic parameters of Saxagliptin, and sildenafil,(AUC0→∞), (AUC0→t); Cmax; tmax; t½, k; ka) will be measured using validated LC-MS/MS method. Therapeutic doses will be given to volunteers as follows: Sildenafil 50 mg single dose on day 1, then washout period from day 2 till day 8. Saxagliptin 5 mg once/day will be given from day 9 till day 12, then on day 13 the two drugs will be co-administered. Blood samples (5ml) for pharmacokinetic analysis will be collected on days 1 and 13 for Sildenafil as well as on days 12 and 13 for Saxagliptin
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age 18-45 years. 2. Ideal weight within the normal range according to accepted life tables. 3. Non-contributory history and normal physiological examination. 4. Laboratory data within normal limits. 5. Performance and compliance. 6. The subjects should be without known history of alcohol or drug abuse problems and should preferably be non-smokers. 7. 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
1. A known hypersensitivity to the drug. 2. Gastrointestinal diseases. 3. Auto immune diseases. 4. Renal diseases or dysfunction. 5. Cardiovascular disease of any type. 6. Pancreatic disease including diabetes. 7. Hepatic disease. 8. Hematological, osteopathic, or pulmonary disease. 9. History of alcoholism or drug abuse. 10. Serious Psychological illness. 11. Positive HIV-I. 12. Smoking (if including they should be identified). 13. Abnormal (out of range) laboratory values. 14. Subject who have taken any medication (Rx or OTC) less than two weeks of the trials starting date. 15. Subject who have donated blood or who have been in multiple dosing studies requiring a large volume of blood (more than 500 ml) to be drawn within six weeks preceding the start of the trials. 16. Any prior surgery of the gastrointestinal tract that may interfere with drug absorption. 17. Treatment with any known enzyme-inducing / inhibiting agents within 30 days prior to the start of the study and throughout the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose. | Maximum Plasma Concentration |
| (AUC0→∞) | pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose. | Area Under Curve Infinity |
| (AUC0→t) | pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose. | Area Under the Curve |
| tmax; | pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose. | Time to reach Maximum concentration |
| T½ | pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose. | Drug half Life |
| Ke | pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose. | Elimination Rate |
| ka | pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose. | Absorption Rate |
| Blood Pressure | measured before dosing and at 2, 4, 6, 8, and 10 hours after drug administration on each day of blood sampling | changes in Systolic and Diastolic Blood Pressure from normal range |
| Heart Rate | measured before dosing and at 2, 4, 6, 8, and 10 hours after drug administration on each day of blood sampling | Changes in heart rate from normal range |
Contacts
Primary ContactRania Y Mansour, MD
Outcome results
None listed