Impact of OCT1 and CYP2D6 Genotypes on Pharmacokinetics of Berberine in Healthy Volunteers
Condition: Pharmacokinetic Study in Healthy Volunteers
Study type: Interventional

Summary: 
      This study should investigate the differences of berberine pharmacokinetic parameters in
      three cohorts of healthy volunteers with distinct genotypes of the organic cation transporter
      1 (OCT1) gene and the cytochrome P450 2D6 (CYP2D6) gene:

      Cohort 1a) OCT1 and CYP2D6 wildtype genotypes n = 10 Cohort 1b) OCT1 and CYP2D6 wildtype
      genotypes n = 10 Cohort 2) OCT1 deficient/CYP2D6 wildtype genotypes n = 10 Cohort 3) OCT1
      wildtype/CYP2D6 deficient genotypes n = 10 Participants will be selected from the study
      volunteers database of the Institute of Pharmacology in Greifswald according to their OCT1
      and CYP2D6 genotypes and to achieve best matching according to sex, age, BMI, alcohol
      consumption and smoking between Cohort 1a and 2 or Cohort 1b and 3, respectively.
    

Detailed description: 
      A single dose of 1000 mg berberine will be administered in two capsules with 250 ml of still
      water in the overnight fasting condition. A total of 12 blood samples will be taken at
      defined time points (baseline, 1; 1.5; 2; 3; 4; 5; 6; 8; 10; 24; 48 h). At each time point,
      blood will be collected in 2x 7.5 ml tubes for collecting serum and plasma samples to
      determine berberine, its metabolites and biomarkers of OCT1 transport and CYP2D6 enzymatic
      activity. At baseline, additional 2x 2.7 ml blood tubes will be collected for DNA isolation.

      The total amount of blood collected for each participant is 190 ml at the three
      Pharmacokinetic Visits and 10 ml at the Screening Visit. Every hour, participants will drink
      100 ml of sparkling water to stimulate intestinal peristalsis and promote transport of the
      capsule. After 2 hours, the participants may drink a cup of tea or coffee and after 4 hours
      they will be served a meal. Urine will be collected during the first 10 h after
      administration. Monitoring of vital parameters, e.g. blood pressure and heart rate, will take
      place for the first 4 hours after administration. The participants will stay in the Clinical
      Research Unit of the Institute of Pharmacology for the first 10 hours after administration.
    

Intervention name(s): Berberine
Intervention type(s): Dietary Supplement
Intervention description(s): A single dose of 1000 mg berberine in two capsules will be administered with 250 ml of still water in the overnight fasting condition. A total of 12 blood samples will be taken at defined time points (baseline, 1; 1.5; 2; 3; 4; 5; 6; 8; 10; 24; 48 h). At each time point, blood will be collected in 2x 7.5 ml tubes for collecting serum and plasma samples to determine berberine, its metabolites and biomarkers of OCT1 transport and CYP2D6 enzymatic activity
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: This study should investigate the differences of berberine pharmacokinetic parameters in three cohorts of healthy volunteers:
Cohort 1a) OCT1 and CYP2D6 wildtype genotypes n = 10 Cohort 1b) OCT1 and CYP2D6 wildtype genotypes n = 10 Cohort 2) OCT1 deficient/CYP2D6 wildtype genotypes n = 10 Cohort 3) OCT1 wildtype/CYP2D6 deficient genotypes n = 10
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Berberine; OCT1; CYP2D6; pharmacogenetic; pharmacokinetic