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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.

Ponsinomycin is a new macrolide. Following oral administration, ponsinomycin is totally metabolized, even before reaching blood circulation. Metabolite Mb12 is the first compound on the main metabolic route, which can be assayed. The influence of food on ponsinomycin bioavailability has therefore been estimated from measurements of Mb12 plasma levels. Twelve young healthy volunteers received 800 mg of ponsinomycin as a syrup on two separate occasions, 2 hours before and during a standard meal. The Mb12 metabolite was assayed in plasma by High Pressure Liquid Chromatography (HPLC). Plasma peak concentrations and areas under curves were not significantly different but time to peak was significantly shorter when ponsinomycin was administered during meal. The results suggest that ponsinomycin absorption is faster when administered with food but quantitatively unchanged.

Ponsinomycin is a new macrolide. Its pharmacokinetics is characterized by an extensive metabolism. Following oral dosing in human, unchanged ponsinomycin is not found in blood, but 3 main metabolites: Mb12, Mb6 and Mb9a can be assayed. Twelve young healthy volunteers received ponsinomycin orally, at doses equal to 400, 800 and 1,200 mg on 3 separate occasions, according to a cross-over design. Metabolites Mb12, Mb6 and Mb9a were measured in plasma by HPLC. The pharmacokinetics of Mb12 was linear in the range of doses administered. A dose-dependent effect leading to a reduction of the apparent elimination rate when dose increased was observed with Mb9a and more importantly with Mb6.

Ambroxol and clenbuterol are two drugs with potential pharmacological synergy. The objective of this study was to compare the apparent bioavailabilities at steady-state of these two compounds administered alone or in combination (CHF-023). Nine healthy male volunteers participated in the study. They received 30 mg of ambroxol alone (one Fluibron tablet), or 20 micrograms of clenbuterol alone (one Spiropent tablet), or 30 mg of ambroxol plus 20 micrograms of clenbuterol in combination (one CHF-023 tablet), every 12 hours for 7 days on three separate occasions. Ambroxol and clenbuterol concentrations were measured in plasma by appropriate GC/MS methods. Pharmacokinetic parameters were calculated by non-compartmental methods and submitted to statistical comparisons. Compartmental analysis was also performed on data provided by CHF-023 treatment. It was concluded that apparent bioavailabilities of ambroxol and clenbuterol are almost identical in Fluibron and CHF-023 tablets, and in Spiropent and CHF-023 tablets, respectively, with no statistically significant differences between pharmacokinetic parameters calculated for these two drugs during different treatments, except for peak concentration of ambroxol.