Pharmacological indices and pulmonary distribution of rifampicin after repeated oral administration in healthy foals
Berlin, A. Kirschbaum, L. Spieckermann, S. Oswald, M. Keiser, M. Grube, M. Venner & W. Siegmund
There is a lack of pharmacokinetic and pharmacodynamic data for rifampicin. In six healthy Warmblood foals, serum concentrations of rifampicin were measured at intervals up to 48 hours following an intravenous bolus of 10 mg/kg bwt rifampicin. Following a 7-day washout period, foals were randomly allocated to groups treated either with 10 or 20 mg/kg bwt rifampicin once daily for 10 days. Serum concentrations were measured at intervals up to 24 hours after the last dose. Bronchoalveolar lavage (BAL) was performed on foals 24 hours after the last oral dose. Liquid chromatography tandem-mass spectrometry was used to determine levels of rifampicin and its active metabolite in plasma, lavage fluid and BAL cells.
At all doses that were tested, plasma concentrations were significantly higher than the minimum inhibitory concentration required. The half-lives of rifampicin were significantly lower following oral dosing compared to intravenous dosing and there was a significantly longer half-life following the 20 mg/kg bwt dose compared to the 10 mg/kg bwt dose. Systemic exposure to rifampicin was greatest with the intravenous dose, followed by 20 mg/kg bwt and then 10 mg/kg bwt dose. Concentrations of rifampicin in BAL fluid and cells were slightly lower than plasma levels measured at the same time point.
This study provided novel pharmacokinetic data for rifampicin and demonstrated that rifampicin penetrates well into the lung following a 10 mg/kg bwt dose once daily. Further research in this area should focus on clinical outcomes for this dosing regime when combined with a macrolide antibiotic for the treatment of Rhodococcus equi infections.