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.

An open study was carried out in ten healthy, male volunteers in order to investigate the renal tolerance of cefpirome (HR 810), a new cephalosporin antibiotic. Subjects received a single dose of 1.0 g of cefpirome and then repeated doses of 1.0 g of cefpirome twice daily for five days. Urine was collected in several fractions during the study and the urine excretion, excretions of creatinine, N-acetyl-beta-D-glucosaminidase, gamma glutamyltransferase, alanine aminopeptidase and lactate dehydrogenase were calculated in 12-hour fractions. Serum creatinine (using an enzymatic method), beta 2-microglobulin concentrations and creatinine clearance were also determined. Based on the findings of these renal enzymes, renal tolerance was good. This was also confirmed by creatinine clearance calculations and follow-up of serum beta 2-microglobulin levels. Cefpirome showed good renal tolerance without any signs of nephrotoxicity in this study with the methods used.

In gonorrhea therapy, cephalosporins are conventionally administered by intramuscular (i.m.) injection, which rather frequently leads to local side effects. To

The pharmacokinetics of cefpirome (HR 810)3-(2,3-cyclopenteno-1-pyridinium)-methyl-7-2-synmethoximino -2-(2- aminothiazol-4-yl)-acetamido-ceph-3-em-4-carboxylate, a new cephalosporin with an extremely broad antimicrobial spectrum, were tested in an open cross-over trial in ten healthy male volunteers using i.v. and i.m. injections of 1 g. Serum concentrations were monitored over 24 h after application, using both chromatographic and microbiological assays. Urine was collected in 2-h fractions for up to 8 h after application, then for 4 h, and thereafter in 12-h fractions for up to 48 h after application. Urine concentrations of the drug were measured by both HPLC and bioassay. The measurements were compared by linear distribution independent regression, and were found to be equivalent, indicating no major antimicrobially active metabolites of HR 810. A two-compartment open model was used for the calculation of pharmacokinetic parameters for both i.v. and i.m. dosing. The median maximum concentration in plasma after i.m. administration was 30.6 mg/l at 1.6 h (HPLC). The elimination half-life times of 1.9 h to 2.1 h did not differ significantly between the two routes investigated. With regard to bioavailability there was no difference between the i.m. and i.v. routes, as demonstrated by the AUC and urinary recovery of unchanged substance. Clinically relevant urine concentrations of cefpirome were detected for at least 12 h after dosing. The general tolerability was good.

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