Phenotyping of CYP3A by Oral Midazolam in Healthy Mazandarani Volunteers (Iran)

Abstract

BACKGROUND AND OBJECTIVE: CYP3A is responsible for hepatic microsomal metabolism of more than 50% of drugs which are its specific substrate. Metabolic activity of this enzyme depends on several factors. Since it has not been done a systematic study of the enzyme activity in Iranian population, this study was conducted to investigate the enzyme activity in a small sample of Mazandarani population (from north of Iran) using midazolam (MDZ) blood levels as an important probe.METHODS: This study was done on 100 Mazandarani healthy volunteers. After recoding individual information (age, sex and weight), subjects were given 100 ml syrup containing 10 mg midazolam. Blood samples were taken after 0.5, 2 and 6 hr after drug administration and plasma concentrations of midazolam were measured using HPLC method. Oral clearance of midazolam (CL/F) as criteria of the enzyme activity was assessed using P-Pharm software.FINDINGS: The mean (SD) of age was 24.5 ± 6.9 years. Eighteen persons were female. All the subjects experienced some degrees of sedation. The mean (SD) of clearance of MDZ was 77.22 ± 20.98 l/h and clearance of MDZ in female (83.79 ± 15.19 l/h) was higher than male (75.68 ± 21.85l/h) (p<0.001). Total volume of distribution (Vd) and elimination half life were 312.65 ± 50.44 and 2.96 ± 0.68, respectively.CONCLUSION: According to the results, a normal phenotype of CYP3A activity was observed in the Iranian participants in this study. The clearance of oral MDZ and/or CYP3A activity is higher in female subjects than in males.

Keywords

• phenotype of cyp3a
• midazolam
• clearance
• hepatic metabolism