Roxithromycin penetration into skin suction blister fluid following multiple doses

Roxithromycin (ROX) concentrations in plasma, skin blister fluid (SBF), and saliva were investigated in six healthy male subjects after administration of 150 mg every 12 hours for 3.5 days (seven doses). Mean peak plasma concentration after the last dose was 5.4 ± 1.3 mg/L (range, 2.8 to 10.0 mg/L) and was attained at a mean time of 1.3 ± 0.2 hours. From the plasma concentration-time curve after the last dose the following pharmacokinetic parameters were calculated: elimination rate constant, 0.043 ± 0.005 L/hr; elimination half-life, 17.5 ± 2.2 hr; area under the concentration-time curve from zero to infinity; 106.4 ± 6.9 mg/L · hr. ROX showed a good penetration into SBF; the mean SBF/plasma concentration ratio ranged from 47% to 106% at two and 24 hours after administration, respectively. The mean penetration ratio of ROX, calculated as the ratio of the areas under SBF and plasma curves, was 63%. The SBF elimiantion half-life could not be calculated due to the lack of a clearly defined terminal elimination phase during the sampling period (24 hours). Saliva levels were always below the detection limit of the assay procedure.