Effect of Ponsinomycin on Single-Dose Kinetics and Metabolism of Carbamazepine

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Abstract
The effect of ponsinomycin (or miocamycin), a new macrolide antibiotic, was investigated on the pharmacokinetics of carbamazepine (CBZ) administered as a single dose in healthy volunteers. Disposition of the active 10, 11 epoxycarbamazepine (ECBZ) was investigated as well. For each compound both total and free plasma concentrations were measured. A moderate (+13%) but statistically significant (p < 0.05) increase of CBZ total area under the curve (AUC), was observed in the presence of ponsinomycin, accompanied by a 26% decrease (p < 0.01) in the AUC of its metabolite. There was a tendency toward an increase in AUC of unbound CBZ, although it was not statistically significant. Together these data suggest that formation of ECBZ is inhibited in the presence of ponsinomycin. The relative importance of the epoxy-diol metabolic pathway being increased at steady state due to autoinduction, results of this study suggest that CBZ plasma levels should be carefully monitored in patients receiving ponsinomycin.