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Metabolites of the cephapirin beta-lactam antibiotic have not previously been reported in bovine milk. The principal metabolite was tentatively identified as desacetylcephapirin by liquid chromatography with UV-VIS photodiode array (LC/UV-VIS PDA), and liquid-chromatography-mass-spectrometric (LC-MS) detection. Synthetic desacetylcephapirin was prepared by incubation of cephapirin in bovine milk and serum at 37 degrees C. Also, a method for determining cephapirin in bovine milk and serum was developed. The detection limits for cephapirin and desacetylcephapirin were estimated to be 10 and 50 micrograms/kg, respectively, for LC/UV-VIS PDA, and 100 and 500 micrograms/kg for LC-MS.

When the antibacterial substances of cephalothin and cephapirin in the serum and urine after intramuscular injection were separated and assayed, desacetyl metabolities of both drugs were detected. These tendencies were especially apparent in the tissue concentrations. When both the drugs were given intravenously to healthy volunteers, the amounts of their desacetyl metabolites were not greater in man than in rats.

A 15 min i.v. infusion supplying either 1 or 2 g of sodium cephapirin was administered preoperatively to patients about to undergo either retropubic or transvesical prostatectomy. Tissue samples were obtained 30 min after the end of the infusion. Blood samples were obtained immediately before the start of the infusion and 30 min after the end of it. Cephapirin levels in the blood averaged 25.9 +/- 4.0 microgram/ml after the 1 g dose and 47.5 +/- 5.6 microgram/ml after the 2 g dose. Drug levels in prostatic tissue averaged 24.5 +/- 7.1 and 25.8 +/- 4.4 microgram/g for the 1 and 2 g doses, respectively. Levels in tissue taken from the seminal vesicle, often the focus of infection in bacterial prostatitis, averaged 12.5 +/- 2.3 and 44.8 +/- 14.9 microgram/g for the 1 and 2 g doses, respectively. These results suggest that bactericidal levels of cephapirin against sensitive organisms can readily be achieved in the prostate and seminal vesicles.

Six healthy adult horse mares were each given a single injection of sodium cephapirin (20 mg/kg of body weight, IV), and serum cephapirin concentrations were measured serially over a 6-hour period. The mean elimination rate constant was 0.78 hour-1 and the elimination half-life was 0.92 hours. The apparent volume of distribution (at steady state) and the clearance of the drug were estimated at 0.17 L/kg and 598 ml/hour/kg, respectively. Each mare was then given 4 consecutive IM injections of sodium cephapirin (400 mg/ml) at a dosage level of 20 mg/kg. Cephapirin concentrations in serum, synovial fluid, peritoneal fluid, CSF, urine, and endometrium were measured serially. After IM administration, the highest mean serum concentration was 14.8 micrograms/ml 25 minutes after the 4th injection. The highest mean synovial and peritoneal concentrations were 4.6 micrograms/ml and 5.0 micrograms/ml, respectively, 2 hours after the 4th injection. The highest mean endometrial concentration was 2.2 micrograms/g 4 hours after the 4th injection. Mean urine concentrations reached 7,421 micrograms/ml. Cephapirin did not readily penetrate the CSF. When cephapirin was given IM at the same dose, but in a less concentrated solution (250 mg/ml), serum concentrations peaked at 25.0 micrograms/ml 20 minutes after injection, but the area under the serum concentration-time curve was not significantly different (P greater than 0.05). The bioavailability of the drug was greater than or equal to 95% after IM injection.

The pharmacokinetics of 3-hydroxymethyl-7-[2-(4-pyridyl-thio)acetamido]-2-cephem-2-carboxylic acid acetate (cefapirin) was evaluated after 1.0 g i.m. to 14 patients with different glomerular and tubular functions. Peaks in normal renal function ranged between 9--17 micrograms/ml and was 3--4 times higher in patients with glomerular filtration rates below 30 ml/min. The serum half-life in normal renal function was 0.8 h and was somewhat increased in renal impairment. The distribution volume was little influenced by renal capacity. Recommendations for dosage are given.

Drug concentrations in plasma and urine were determined in 5 healthy subjects after intravenous infusion of 1 gm cephapirin and cephaloridine. Sampling of blood and urine was frequent and prolonged. Specimens were analyzed by high-pressure liquid chromatography (HPLC). Renal clearance of cephapirin decreased to less than 5% of control in all subjects when drug concentrations in plasma and urine declined. Cephaloridine clearance decreased to a lesser extent. Our findings suggest that, besides tubular secretion and glomerular filtration, a saturable and probably active tubular reabsorption is also involved in the renal handling of these two cephalosporins. The saturable reabsorption process was characterized by its Michaelis-Menten constant Km and its maximum transport capacity Tm.

The levels of three antibiotics (Cefapirin, Doxycycline, Gentamicin) were studied in an experimental model (swimming stress) with elevated serum FFA. Sixty Wistar rats were in three groups used divided. Each group consisted of 3 subgroups. The subgroups A and B were submitted in swimming stress procedure for 10 and 20 days. The subgroup C was the control group. Since stress increases the FFA the concentration of antibiotics in blood and bone are influenced. According to the estimation of the result the following were observed: 1) Increase of FFA in stress groups 2) Weight increase of adrenals in stress groups which means that the stress procedure was effective 3) Increase of cefapirin level 4) Increase of doxycyclin 5) Increase of gentamicin 6) Increase of haematocrite.

Cephapirin (20 mg/kg of body weight, IV) was administered before and after 3 doses of probenecid (25, 50, or 75 mg/kg, intragastrically, at 12-hour intervals) to 2 mares. Clearance and apparent volume of distribution, based on area under the curve, were negatively correlated with probenecid dose. Clearance of cephapirin was decreased by approximately 50% by administration of 50 mg of probenecid/kg. Serum, synovial fluid, peritoneal fluid, CSF, urinary, and endometrial concentrations of cephapirin were determined after 5 doses of cephapirin (20 mg/kg, IM, at 12-hour intervals) without and with concurrently administered probenecid (50 mg/kg, intragastrically) to 6 mares, including the 2 mares given cephapirin, IV. Highest mean serum cephapirin concentrations were 16.1 +/- 2.16 micrograms/ml at 0.5 hour after the 5th cephapirin dose [postinjection (initial) hour (PIH) 48.5] in mares not given probenecid and 23.7 +/- 1.30 micrograms/ml at 1.5 hours after the 5th cephapirin dose (PIH 49.5) in mares given probenecid. Mean peak peritoneal fluid and synovial fluid cephapirin concentrations were 6.2 +/- 0.57 micrograms/ml and 6.6 +/- 0.58 micrograms/ml, respectively, without probenecid administration and 12.3 +/- 0.46 micrograms/ml and 10 +/- 0.78 micrograms/ml, respectively, with concurrent probenecid administration. Mean trough cephapirin concentrations for peritoneal and synovial fluids in mares given probenecid were 2 to 3 times higher than trough concentrations in mares not given probenecid. Overall mean cephapirin concentrations were significantly higher for serum, peritoneal fluid, synovial fluid, and endometrium when probenecid was administered concurrently with cephapirin (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on absorption and excretion of cephapirin (CEPR) are described. CEPR was administered by intravenous drip infusion to 4 healthy volunteers weighing 53 kg to 61 kg, and the serum levels were measured. Pharmacokinetic parameters were calculated by one-compartment model and two-compartment model. Each model was comparatively applied to every founds. Most appropriate administration rate of intravenous drip infusion was discussed due to calculated serum levels, therapeutic AUC and effective time.

Since the discovery of cephalothin in 1962, many semi-synthetic cephalosporins have appeared. To choose the most suitable drug for the clinical treatment of infections, the characteristics of these antibiotics must be sufficiently understood. When cephalosporins which are or will be commercially available are divided into two categories, one consists of cephaloridine, cefazolin and cephalexin which are comparatively stable in the living body; and the other cephalothin, cephaloglycin, cephapirin and cephacetrile which are metabolized into desacetyl compounds with low antibacterial activity. In this study, the author compared the absorption, excretion and some other properties of cefazolin and cephalothin, (widely used clinically), and cephapirin (still under study in Japan).

The microbiological properties of cephapirin, a new semisynthetis cephalosporin, have been studied. This antibiotic, if compared with ampicillin, shows a greater activity against gram positive bacteria, a lack of sensitivity to staphlococcal beta-lactamase, and a lower sensitivity to those produced by gram-negative bacteria. Useful therapeutic of cephapirin levels can be detected in human serum 6 h after administration of 500 and 1,000 mg parenterally.

The diffusibility of bacampicillin, ampicillin, cephalothin, and cephapirin into human interstitial fluid was investigated by using crossover studies. We compared bacampicillin with ampicillin and found that bacampicillin was better absorbed after oral administration. Blood, interstitial fluid, and urine levels were consistently higher in volunteers who received bacampicillin. We compared cephalothin with cephapirin and found that blood and interstitial fluid levels were comparable throughout the study.

Circulation of 2 semi-synthetic cephalosporins, i. e. cephazoline and cephapyrine in the blood of rabbits after their intramuscular administration in single doses of 5 and 20 mg/kg was studied. It was found that the antibiotics were well adsorbed into the blood. Their maximum blood levels were achieved 15--30 minutes after administration. Cephazoline provided a higher blood level persisting for longer periods of time as compared to cephapyrine. The value of the time of the two-fold decrease in the cephazoline blood level was higher. A four-fold increase in the dose of the cephalosporines resulted in an increase in their blood levels but did not induce any significant increase in the time of their circulation.

Antibiotics' level was estimated in mandible and serum of wistar albino rats with and without co-administration of phenylbutazone, 5 groups of animals were used. The animals of group A were injected with 1 g/kg ampicillin and these of group B 1g/kg ampicillin and 100 mg/kg phenylbutazone im. To the animals of group C cephapirin was given 1 g/kg and these of group D 1g/kg cephapirin with 100 mg/kg phenylbutazone. The animals of group E were injected only with phenylbutazone. All the drugs, were given at a single dose. The level of antibiotics was estimated in serum and in mandible with the method of minimal inhibitory concentration (MIC). An increase of the levels of antibiotics (ampicillin, cephapirin) was observed in those groups (B, D) to the animals of which phenylbutazone was given (together with antibiotics), compared with the groups (A, C) which had received antibiotics alone.

An anion-exchange column technique for extraction of antibiotics from serum proteins has been developed for use in the assay of cephapirin, cefotaxime, and cefoxitin by high-pressure liquid chromatography. Anion-exchange extraction of cephapirin from serum samples by this technique was compared with protein precipitation methods, using 6% trichloroacetic acid or absolute ethanol. Column extraction gave improved quantitative drug recovery and reduced background serum interferences in the resultant chromatograms when evaluated against protein precipitation. Comparisons of this method with microbiological assay gave statistically equivalent results. Twelve patient samples were assayed for cephapirin, and no interferences were encountered from the 22 systemic agents these subjects were receiving. The anion-exchange technique for antibiotic extraction provides a rapid, precise, and quantitative antibiotic assay when used with liquid chromatography.

The penetration of cephapirin sodium into tissues that are commonly involved in gynecologic infections was studied after administration of a single i.v. dose of 1 g of cephapirin to about 15 patients to undergo gynecologic surgery. Blood and tissue specimens were obtained either 30 or 60 min after the infusion had been completed. Blood levels averaged 16.07 +/- 3.7 and 6.29 +/- 1.6 microgram/ml and mean tissue levels were 7.87 and 6.28 microgram at these two sampling times, respectively. These results suggest that bactericidal levels of cephapirin against sensitive organisms can be achieved in gynecologic tissues.

Six healthy foals, from 4 to 6 days of age, were given a single IM injection of sodium cephapirin (250 mg/ml) at a rate of 20 mg/kg of body weight. Serum concentrations of cephapirin were measured serially over an 8-hour period. The mean peak serum concentration was 21.2 micrograms/ml at 10 minutes. The overall elimination rate constant was 1.06/hr and the elimination half-life was 0.70 hour. The apparent volume of distribution at steady state was 1.06 L/kg and plasma clearance was 1,105 ml/hr/kg.

Six patients undergoing chronic hemodialysis and 10 patients with chronic renal insufficiency hospitalized for nondialytic therapy received 1.0 g of cephapirin sodium by the intravenous route. The concentrations of cephapirin in arterial and venous plasma, dialysate, venous blood, and urine were measured during the ensuing 6 hr. The serum half-life of cephapirin was 105 to 108 min for the dialyzed patients and 95.9 min for the nondialyzed patients. Dialysis removed 22.8% of the administered dose. Nondialyzed patients excreted 19.5% of the administered dose in the urine. The concentration of cephapirin in the urine of all nondialyzed patients exceeded 50 mug/ml. The recovery of cephapirin in the urine collected for 6 hr after injection was from 34 to 770 mg (mean 195 mg). To maintain a concentration of cephapirin in the blood and urine which exceeds the minimal inhibitory concentration for most gram-positive and gram-negative microorganisms, nondialyzed patients should receive 15 to 18 mg of cephapirin per kg every 12 hr. Dialyzed patients should receive the same dose just prior to dialysis and every 12 hr thereafter.