Influence of Ethnicity and ABCB1 Gene Polymorphism on the Pharmacokinetics of Azithromycin in Healthy Bangladeshi Volunteers

• Status: Recruiting
• Trial end date: 2022-07-01
• Target enrollment: 0
• Participant gender: All

Summary

It is well recognized that different patients respond in different ways to the same medication. These differences are often greater among members of a population than they are within the same person at different times (or between monozygotic twins). The existence of large population differences with small interpatient variability is consistent with inheritance as a determinant of drug response; it is estimated that genetics can account for 20 to 95 percent of variability in drug disposition and effects. Azithromycin is frequently used worldwide irrespective of gender or ethnic populations therefore, to investigate the impact of gender and ABCB1 gene polymorphism holds clinical significance. As a correlation between azithromycin high plasma level and cardiac arrhythmia also exists . If we can prove the variation of pharmacokinetics of azithromycin due to ethnic differences and ABCB1 polymorphism dose adjustment can be done.

No relevant study regarding this has been done before in Bangladesh. Therefore, this preliminary study would be of great benefit to formulate the individualized doses regiment design which may improve the efficacy of drug while reducing adverse reaction. At the same time, Genotyping may prove an essential tool for individualized treatment by optimizing the drug dosage for an individual's genetic variability. Further study regarding pharmacogenetics of various drugs may be possible in our country in the future .The present study design to investigate the influence of ethnic difference and gene polymorphism on the pharmacokinetics of azithromycin in Bangladeshi Bangalee and Bangladeshi minor ethnic volunteers.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
• Treatments: Azithromycin

Criteria

Inclusion Criteria: 1. Healthy Bangladeshi male and female subjects, between the ages of 20 and 25 years. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure (BP) and pulse rate (PR) measurement, 12-lead ECG, routine laboratory tests (Blood chemistry, hematology and urine analysis).

2. BMI of 18 to 28 kg/m2; and a total body weight ≥50 kg for males and ≥45 kg for females.

3. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.

4. Subjects must be the residence of Chittagong Hill Tracts by birth.

-

Exclusion Criteria:

1. Liver cirrhosis.

2. Chronic renal failure. .

3. History of gastrectomy.

4. History of drug abuse within the past 5 years.

5. Treatment with an investigational drug within 3 months preceding the first dose of investigational product.

6. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the subject's eligibility.

7. Screening supine 12-lead ECG demonstrating a corrected QT (QTc) interval >450 msec or a QRS complex >120 msec. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or QRS values should be used to determine the subject's eligibility.

8. Female subjects who are breastfeeding or with positive pregnancy test at Screening and during the study period.

9. Use of prescription or nonprescription drugs, dietary supplements and herbal medicines within 14 days prior to Screening.

10. Blood donation (excluding plasma donations) or loss of blood of approximately 450 mL or more within 3 months prior to Screening.

111. History of hypersensitivity to azithromycin or any components of its formulation.

112. Use of special diet (including dragon fruit, grape fruit juice, mango, citrus, etc.), strenuous activities or other factors that may affect the disposition of the study medication within 14 days prior to Screening.

13. Use of chocolate, food or beverages containing caffeine or xanthine within 48 hours prior to dosing.

14. Use of products containing alcohol within 48 hours prior to dosing. 15. History of HIV, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, HCVAb..

16. Schizophrenia or other psychiatric illness..

-