Single oral dose pharmacokinetics of the two main components of pristinamycin in humans

A preliminary study of the pharmacokinetics of the two main components of pristinamycin, PIA and PIIA is reported. A single oral dose of 2 g of pristinamycin was administered to six patients with normal renal and hepatic function. The samples were withdrawn during 9.5 h and assayed by HPLC. PIA and PIIA plasma levels evolved in parallel in each subject and their kinetic parameters were comparable: Tmax of 3.25 +/- 1.80 h and 3.08 +/- 1.98 h, Cmax of 0.760 +/- 0.427 mg/l and 0.581 +/- 0.285 mg/l, elimination half-life of 4.03 +/- 2.77 h-1 and 2.83 +/- 0.75 h-1, respectively. The relative proportions of PIA and PIIA, which govern the antibacterial activity of the mixture, were maintained during the study in the range of values leading to 90-100% of optimal activity against Staphylococcus aureus. The sum of the plasma concentrations of PIA and PIIA, which can be considered to be equivalent to the concentration of total pristinamycin, was superior to the MICs for the most susceptible staphylococcal strains during the entire period of study. On the other hand, the sum of PIA and PIIA concentrations exceeded the MICs for the less susceptible strains for only 4 h. These results differ from the scanty pharmacokinetic data presently available, which were obtained by microbiological methods.