Cefodizime penetration into skin suction blister fluid following a single intravenous dose

Abstract

Cefodizime pharmacokinetics was investigated, evaluating drug concentrations in serum, skin suction blister fluid (SBF), saliva and urine in six healthy male subjects who were administered a 1-g dose intravenously. Serum levels in five subjects can be described according to a two-compartment open model; terminal half-life is 181 +/- 14 min. Volume of distribution (Vd beta) amounts to 15.3 +/- 1.61, serum clearance to 59 +/- 6 ml/min, renal clearance to 33 +/- 3 ml/min. Of the administered dose, 54% is renally excreted unchanged within 27 h. Unbound drug fraction in serum is 19.0% and in SBF 38.4%. Thus renal clearance of free cefodizime amounts to 172 ml/min, Vdss to 68.9 l (free drug). Whereas cefodizime has not been detected in saliva samples, SBF concentration 3-9 h post administration parallel serum levels, amounting to 40% of the respective serum concentration. At 9 h, unbound cefodizime concentrations in SBF amount to 1.4 +/- 0.4 micrograms/ml, this value being well above the MIC90% values of many clinically relevant bacteria.