SUCTION-INDUCED BLISTER FLUID PENETRATION OF CEFDINIR IN HEALTHY-VOLUNTEERS FOLLOWING ASCENDING ORAL DOSES

The pharmacokinetics and suction-induced blister fluid penetration of cefdinir following single oral administrations of 200, 300, 400, and 6 00 mg were studied in 16 healthy young male volunteers according to a Latin square design. Plasma, blister, and urine samples were assayed b y high-pressure liquid chromatography. We observed a nonlinear relatio nship (P = 0.02) between the dose and the maximum concentration in pla sma as well as between the dose and the area under the concentration-t ime curve (AUG) in plasma (P < 0.001), which may be indicative of a li mited absorption process. This resulted in a lower AUC value than expe cted as well as a smaller fraction of cefdinir excreted unchanged at a dose of 600 mg. Renal clearance decreased with increasing doses (P < 0.006; analysis of variance with the Latin square design and Games-How ell procedure). Maximal cefdinir concentrations in blister fluid were delayed compared with concentrations in plasma. Blister fluid penetrat ion measured by the ratio of the AUC in blister fluid to the AUC in pl asma was extensive (92.4 to 108.4%). Cefdinir concentrations in bliste r fluid remained equal to or higher than the concentrations in plasma from 6 to 12 h following cefdinir administration. On the basis of the concentrations in blister fluid and the in vitro MIC data, we estimate d that cefdinir at 200 to 400 mg administered twice daily would be ade quate to treat uncomplicated skin infections caused by Streptococcus p yogenes. Seven volunteers experienced episodes of light-to-moderate di arrhea. These adverse events occurred irrespective of dose.