NCT03990129

Pharmacokinetic Interactions of Metamizole (Dipyrone) in Healthy Subjects

Single-center, Open, Controlled Study to Investigate the Interaction of Metamizole With the Cytochrome p450 System in Healthy Subjects by Application of the Basel Cocktail

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: University Hospital, Basel, Switzerland · Academic / Other
• Sex: Male
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

Investigators conducted a single center, two-phased, open, controlled pharmacokinetic study to investigate the drug-drug interaction potential of metamizole. For this reason, healthy male volunteers were screened. Enrolled participants were phenotyped on day 1 using the Basel Cocktail (phenotyping cocktail containing specific substrates for CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4). After, they received metamizole treatment for 8 days (3 grams per day). On the 8th day (day 9), they were phenotyped again with the Basel Cocktail and the respective phenotypes (d1 vs. d9) were compared.

Detailed description

12 healthy male subjects meeting the inclusion and exclusion criteria were enrolled. On day 1, they ingested a capsule containing the Basel Cocktail (1A2: caffeine, 2B6: efavirenz, 2C9: flurbiprofen, 2C19: omeprazole, 2D6: metoprolol, 3A4: midazolam) in fastened state. Blood samples were withdrawn over 24 hours and the AUC ratios between metabolite and parent were calculated to determine the phenotype. Probands began metamizole treatment (3000 mg/day) at the day of the 24h measurement. After 3-4 day, probands were returning to the facility to ensure safety during the metamizole treatment, blood cell count and metamizole metabolites were measured. After the 7 days of treatment, probands were exposed again to the Basel Cocktail in a fastened state. Probands were still exposed to metamizole to ensure potential inhibition. 24 hours plasma samples were withdrawn, area under the curve (AUC) ratios were calculated and compared to the basal state. After an end of study visit on the day of the 24h blood sample (following the second study day), probands were discharged.

Conditions

• Inhibition
• Induction
• Drug-Drug Interaction

Interventions

Type	Name	Description
DRUG	Metamizole	One week treatment with metamizole (500 mg tablets, 2-2-2)

Timeline

• Start date: 2018-09-04
• Primary completion: 2018-10-31
• Completion: 2018-10-31
• First posted: 2019-06-18
• Last updated: 2019-06-20

Locations

1 site across 1 country: Switzerland