Pharmacokinetics of ponsinomycine with repeated ingestion in healthy volunteers
Couet, W.; Reigner, B.G.; Ingrand, I.; Girault, J.; Istin, B.; Bizouard, J.; Fourtillan, J.B.
Therapie 45(2): 105-109
1990
ISSN/ISBN: 0040-5957 PMID: 2353325 Document Number: 354811
Ponsinomycin or miocamycin (MOM) is a new macrolide which is totally metabolized in vivo. The disposition of its 3 major metabolites (Mb12, Mb6 and Mb9a), was investigated following multiple dosing with ponsinomycin at a dose of 800 mg every 12 h, for 8 days, in healthy volunteers. Drug measurements were conducted by high performance liquid chromatography. In agreement with the low values of their apparent elimination half-lives, respectively less than 1.5 h and 3.0 h, metabolites Mb12 and Mb9a did not accumulate with time. Their pharmacokinetics was apparently stable with time. Conversely Mb6 did accumulate, by approximatively a factor 2, although its apparent elimination half-life was only close to 2 h. This value must therefore be considered with caution. A dose dependency effect was previously observed, Mb6 pharmacokinetics could be non linear with time as well. The relative importance of this metabolite is therefore greater at steady-state, following multiple administration than after single dosing with ponsinomycin.