Direct quantitative determination of optically active absorbing drugs in human urine by circular dichroism. Simultaneous direct determination of beta-lactam antibiotics and proteins.

Over 200 urine samples from 61 subjects were analyzed by circular dichroism spectroscopy. The results proved that this technique can be applied to the direct determination of optically active absorbing drugs in urine of subjects under multiple drug administration, independently of the presence of proteins, which can simultaneously be determined. A list of noninterfering drugs is included. The validity of the present method was confirmed by analysis of variance, the beta-lactam antibiotics ampicillin, cefoxitin, and cephalexin being chosen as model drugs and human albumin as the analytical standard for protein determination. The results demonstrated that the proposed method is accurate and precise, the correlation coefficients being higher than 0.9996. A circular dichroism and HPLC data comparison was successfully performed. The principal advantages of this method are simplicity, quickness, and economy, no derivatization or chromatographic separation steps being needed.

Cefoxitin interferes with the "Clini-Skreen" column method for urinary 17-hydroxycorticosteroids.

Cefoxitin interferes with determination of urinary 17-hydroxycorticosteroids. The apparent concentration of hormone is increased from three- to 10-fold in samples from patients receiving cefoxitin when the Amberlite XAD-2 "Clini-Skreen" column is used. To determine the mechanism of interference, we reacted aqueous solutions of cefoxitin, cortisol, cortisone, and 11-deoxycortisol with phenylhydrazine; recorded the adsorption spectra; and determined the molar absorptivities and the equilibrium and rate constants. Also, we recorded the absorption spectra of phenylhydrazine with eight other cepha antibiotics and benzylpenicillin. Cortisol, cortisone, 11-deoxycortisol, and cefoxitin react with phenylhydrazine and absorb light with superimposable spectra and absorption maxima of 410 nm. The other antibiotics react with phenylhydrazine but absorbance maxima of the products vary, none being at 410 nm. Cortisol, cortisone, and 11-deoxycortisol react with phenylhydrazine 35-fold faster, have equilibrium constants ninefold greater, and have molar absorptivities 1.6 times that of cefoxitin. Thus, cefoxitin interferes with determination of urinary 17-hydroxycorticosteroids by forming a chromophore with the same absorbance maximum and with a molar absorptivity similar to cortisol, but much more slowly.

Rapid HPLC analysis of cefoxitin in plasma and urine.

A rapid, specific and precise method is described for the analysis of cefoxitin in plasma and urine by reversed-phase, high performance liquid chromatography (HPLC). Cefoxitin and the internal standard, 3-isobutyl-l-methyl xanthine are eluted after 5.3 and 7.5 min, respectively. The assay sensitivity limit is 1 to 2 mg/l of cefoxitin sodium at 254 nm. Commonly prescribed antibiotics do not interfere. The assay is suitable for routine monitoring and pharmacokinetic studies of cefoxitin.

Effect of orally administered probenecid on the pharmacokinetics of cefoxitin.

To characterize the effect of orally administered probenecid on the pharmacokinetics of cefoxitin in healthy male volunteers, we administered to one group of six subjects 2 g of cefoxitin by intravenous (i.v.) bolus either alone, with 1 g of probenecid concomitantly, or when 1 g of probenecid was administered 1 h previously by using a crossover design. Likewise, we administered to a second group of six subjects 2 g of cefoxitin intramuscularly (i.m.) together with 1 and 2 g of probenecid. Probenecid increased the mean terminal half-life and the area under the serum cefoxitin concentration-time curve (AUC0-24) and decreased renal clearance, but did not alter the volume of the central compartment or the total urinary recovery of i.v.-administered cefoxitin; pretreatment with probenecid produced a greater increase in cefoxitin AUC0-24 and a constant decrease in renal clearance compared to concomitant probenecid. The AUC0-24 after i.m.-administered cefoxitin was greater after 2 g than 1 g of probenecid; the AUC0-24 after i.v.-and i.m.-administered cefoxitin was similar after 1 g of probenecid was given concomitantly. Cefoxitin AUC0-24 was increased further when 1 g of probenecid was given before i.v.-administered cefoxitin or when 2 g of probenecid was given with i.m.-administered cefoxitin. The effect of probenecid was related to both timing and dose.

Cefoxitin, a semi-synthetic cephamycin antibiotic. Metabolism in rats with renal insufficiency.

The metabolism of cefoxitin, a new semi-synthetic cephamycin antibiotic, in rats with renal insufficiency was examined in comparison with that in control. Ascending urinary tract infection was produced in rats by intra-cystic inoculation with a virulent strain of Escherichia coli. In rats with severe infection progressed into purulent inflammation in the pelvis and medullar and cortical abscess formation, the urinary excretion of the antibiotic was reduced till the first 2 h after an i.v. dose of 40 mg/kg, while its serum levels and biliary excretion during this period were contrarily higher than those in rats with mild infection limited to pelvic inflammation and in control. On the other hand, in rats with renal arteriarctia produced by constriction of the renal artery with silver clip, blood levels of the antibiotic were higher than those in control. In the former animals, the urinary excretion was reduced to about a half, while the biliary excretion was increased up to twofold of that in control through the whole experimental period. In animals either with severe infection or with renal arteriarctia, the total recovery in the urine and the bile during 6 h of the experimental period was almost equal to those in mild infection or control groups.