Metformin and daclatasvir: absence of a pharmacokinetic–pharmacodynamic drug interaction in healthy volunteers

AIM

The aim of this study was to evaluate the effect of the proposed organic cation transporter (OCT) inhibitor daclatasvir on the pharmacokinetics and pharmacodynamics of the OCT substrate metformin.

METHODS

This was an open-label, two-period, randomized, crossover trial in 20 healthy subjects. Treatment A consisted of metformin and treatment B consisted of metformin + daclatasvir. Pharmacokinetic curves were recorded at steady state. Geometric mean ratios (GMRs) with 90% confidence intervals (CIs) were calculated for metformin area under the concentration-time curve from 0 to 12 hours (AUC_0–12), maximum plasma concentration (C_max) and final plasma concentration (C_last). An oral glucose tolerance test was performed, measuring insulin, glucose and lactate levels.

RESULTS

The GMRs (90% CI) of metformin AUC_0–12, C_max and C_last (B versus A) were 109% (102–116%), 108% (101–116%) and 112% (103–122%). The GM AUC_0–2 for insulin, glucose and lactate during treatment A and B were 84 and 90 h^.mE/L, 13.6 and 13.4 h^.mmol/L and 3.4 and 3.5 h^.mmol/L, respectively.

CONCLUSIONS

Bioequivalence analysis showed that daclatasvir does not influence the pharmacokinetics of metformin in healthy subjects. Pharmacodynamic parameters were also comparable between treatments.

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