Comparative pharmacokinetics and serum inhibitory activity of clindamycin in different dosing regimens

The comparative pharmacokinetics and serum inhibitory effects of clindamycin were evaluated in six healthy male subjects given multiple-dose infusions of the following regimens in a crossover fashion: 600 mg every 6 h, 900 mg every 8 h, and 1,200 mg every 12 h. Serial blood samples were obtained after the last dose in each regimen and analyzed for clindamycin by a sensitive and specific high-performance liquid chromatography assay technique. Clindamycin pharmacokinetics were estimated by using noncompartmental methods, and serum inhibitory titers were serially determined against Bacteroides fragilis ATCC 25285 and evaluated by using area under the serum inhibitory curve (AUIC). Maximum and minimum concentrations in plasma averaged 12.2 +/- 1.6 and 1.2 +/- 0.6, 16.3 +/- 4.0 and 0.9 +/- 0.5, and 16.8 +/- 2.5 and 0.4 +/- 0.2 micrograms/ml for the 600-, 900-, and 1,200-mg regimens, respectively. Clindamycin plasma clearance and elimination half-life averaged 23.3 +/- 4.0 liters/h and 1.9 +/- 0.4 h for the 600-mg regimen, 25.6 +/- 8.2 liters/h and 2.1 +/- 0.4 h for the 900-mg regimen, and 26.4 +/- 4.7 liters/h and 2.1 +/- 0.4 h for the 1,200-mg regimen. These results were not significantly different. Apparent volume of distribution increased significantly for the 1,200-mg regimen compared with the 600-mg regimen. Mean maximum reciprocal serum inhibitory titers were 96 +/- 35, 101 +/- 43, and 160 +/- 78 for the 600-, 900-, and 1,200-mg regimens, respectively. Minimum reciprocal serum inhibitory titers averaged 12 +/- 4, 6 +/- 3, and 5 +/- 2 for the low-, medium-, and high-dose regimens, respectively. Mean AUIC increased roughly in proportion to dose. Similar daily values for the area under the concentration-time curve and for AUIC for each of the regimens suggest similar daily drug exposure and serum inhibitory activity. A regimen of 1,200 mg every 12 h may represent an alternative dosing strategy for clindamycin.