Pharmacokinetic evaluation of two dosage regimens of clindamycin phosphate

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Abstract
Interpretation of the majority of data on the disposition of clindamycin is confounded by the presence of active metabolites, which may interfere with commonly employed bioassays. We undertook a multiple-dose study of the disposition of clindamycin phosphate and clindamycin, given either as 600 mg intravenously every 6 h or 1,200 mg intravenously every 12 h for five and three doses, respectively, in six healthy volunteers. Concentrations in serum and urine were analyzed by a specific gas chromatography assay. Maximum and minimum clindamycin concentrations in serum and the area under the serum concentration-time curve following the first dose were similar to those observed at the steady state. The mean and standard deviation of the maximum, 1-h postdose, and minimum concentrations in serum at steady state for the 600-mg dose given every 6 h were 16.8 +/- 6.0, 7.6 +/- 0.7, and 2.3 +/- 0.9 microgram/ml, whereas for the 1,200-mg dose given every 12 h they were 17.2 +/- 3.5, 9.8 +/- 1.5, and 0.6 +/- 0.3 microgram/ml, respectively. For the 12-h regimen, clindamycin concentrations in serum remained above 2 micrograms/ml for 7 h. The decay of clindamycin phosphate levels in serum was rapid, with virtually 100% of the phosphate eliminated within the first 1.5 h following the dose. Approximately 0.35 and 4.5% of the administered dose were recovered in the urine as clindamycin phosphate and clindamycin, respectively. Further pharmacokinetic evaluation of the 12-hourly dosage regimen should be done before clinical evaluation in infected patients is undertaken.