Determination of piperacillin and mezlocillin in human serum and urine by high-performance liquid chromatography after derivatisation with 1,2,4-triazole.

High-performance liquid chromatographic methods have been developed for the determination of piperacillin and mezlocillin in human serum and urine samples. The methods involve ultrafiltration of samples followed by reaction with 1.5 M 1, 2, 4-triazole and 0.5 x 10(-3) M mercury (II) chloride in solution (pH 8.50) at 50 degrees C for 15 min. The resulting products were separated on a C18 column following stabilisation in an eluent containing sodium thiosulphate. They were detected at 323 nm for both penicillins. The methods have been applied to assays applied to assays of these penicillins in human serum and urine samples. The procedures, which permit the determination of penicillin concentration down to 0.1 microgram m1-1 in serum and 1 microgram m1-1 in urine samples, are specific to intact penicillins without interference from corresponding penicilloates [see J. Haginaka et al., Anal. Sci. 1 (1985) 73]. At concentrations of 1-500 micrograms ml-1 for each compound, the within- and between-day precisions were 1.8-4.8 and 3.7-6.9, respectively. The accuracy was ca. 100% for all samples assayed.

Alteration in the pharmacokinetic disposition of ciprofloxacin by simultaneous administration of azlocillin.

Healthy subjects were given single intravenous doses of ciprofloxacin, azlocillin, and the two drugs simultaneously on separate occasions. High-pressure liquid chromatographic analysis was used to assay the concentrations of both drugs in serum and urine. Pharmacokinetic parameters were calculated by noncompartmental methods. The total body (CL), renal (CLR), and nonrenal (CLNR) clearances; steady-state volume of distribution (Vss); and fractional urinary excretion of ciprofloxacin were all markedly decreased with the simultaneous administration of azlocillin. The disposition of azlocillin was unchanged when it was given with ciprofloxacin compared to when it was given alone. The pharmacokinetic parameters (mean +/- standard deviation) of ciprofloxacin given alone versus in combination with azlocillin were as follows: CL, 52.2 +/- 9.2 versus 33.9 +/- 6.0 liters/h (P less than 0.0005); CLR, 26.5 +/- 4.8 versus 16.2 +/- 4.2 liters/h (P less than 0.0005); CLNR, 25.8 +/- 5.5 versus 17.7 +/- 4.0 liters/h (P less than 0.03); Vss, 224 +/- 30 versus 166 +/- 41 liters (P less than 0.01); fractional urinary excretion, 0.56 +/- 0.06 versus 0.43 +/- 0.04 (P less than 0.002), respectively. This interaction resulted in significantly higher and more prolonged concentrations of ciprofloxacin in serum, which may be beneficial in the treatment of serious gram-negative bacterial infections, but it could also produce greater toxicity or result in more pronounced effects on oxidative drug metabolism of other medications.

An unforeseen complication of home parenteral antibiotic therapy.

Increasing pressure to cut the length of hospital stay has resulted in a large number of patients receiving home parenteral antibiotic therapy. We present a case of an immediate allergic reaction in a penicillin-sensitive spouse of a patient receiving parenteral mezlocillin sodium therapy. A seminal level of 42 micrograms/mL of mezlocillin was documented by bioassay.

Mezlocillin in pleural effusions--analysis by HPLC.

Mezlocillin concentrations in the pleural fluid of six patients (42-76 years of age, suffering from cytologically confirmed malignant pleural effusions) were determined after intravenous infusion of 10 g mezlocillin. Serum and pleural fluid samples were withdrawn 15, 30, 45, 60 min, 2, 4, and 8 h post infusion. Detection of mezlocillin and its metabolites penicilloic acid and penilloic acid was carried out by means of high performance liquid chromatography (HPLC). Mezlocillin concentrations in serum increased up to 778 +/- 270 micrograms/ml after 15 min, steadily decreasing to 55 +/- 50 micrograms/ml (8 hours post infusion) comparable to the known pharmacokinetic behaviour of mezlocillin; in the pleural effusions mezlocillin levels increased up to 100 +/- 38 micrograms/ml after 1 h. This concentration was maintained throughout the following 7 h. Penicilloic levels ranged about 2-4% within serum, whereas levels below 1% were measured in the pleural fluid.

Assessment of antimicrobial penetrance into the pancreatic juice in humans.

The penetrance of mezlocillin, metronidazole and trimethoprim-sulfamethoxazole into the pancreatic juice of humans was measured in ten patients convalescing from acute pancreatitis at the time of endoscopic retrograde cholangiopancreatography. Therapeutic levels were obtained in the serum for all three antimicrobial agents; simultaneously aspirated nonbile stained pancreatic juice contained therapeutic levels of metronidazole and trimethoprim-sulfamethoxazole. Mezlocillin was not present in a therapeutic level in any patient with nonbile stained pancreatic fluid.

Determination of mezlocillin and its penicilloate and penilloate by high-performance liquid chromatography and stability of mezlocillin at different temperatures.

A method is described for the determination of mezlocillin and its metabolites penicilloic acid and penilloic acid in biological fluids by high-performance liquid chromatography. The stability of mezlocillin in serum and buffer was studied at different temperatures (4, -20, -70, and -196 degrees C) over a period of 6 months. Mezlocillin remained stable at -70 and -196 degrees C, whereas degradation was observed at -20 and 4 degrees C in serum and buffer.

High-performance liquid chromatography analysis of mezlocillin, piperacillin, their degradation products, and of ioxitalamic acid in plasma and urine of healthy volunteers.

In plasma and urine of 10 healthy volunteers after intravenous administration of 4 g mezlocillin and piperacillin, respectively, the parent compounds as well as degradation products were assayed by high-performance liquid chromatography. Ioxitalamic acid, a renal contrast medium, was administered simultaneously, in order to measure the glomerular filtration rate, and to control the collection of 24-h urine. As metabolite of mezlocillin the corresponding penicilloic acid only was found, whereas in the case of piperacillin a further degradation product was observed. Half of the doses given was recovered in the urine as unchanged drugs, and in addition 5-10% as metabolites. No differences were found in the pharmacokinetic behaviour of both antibiotics.

Mezlocillin concentrations in human aqueous humour after intravenous and subconjunctival administration.

27 patients received either 4 g intravenous infusion 1-3 h or 100 mg subconjunctival application of mezlocillin 1-12 h before cataract extraction. After intravenous administration the mean aqueous humour concentration of mezlocillin was 2.9 micrograms/ml after 2 h. The subconjunctival dose produced a mean aqueous humour concentration of 23 and 2.6 micrograms/ml after 3 and 12 h, respectively. These levels are above the minimum inhibitory concentration of mezlocillin for sensitive organisms.

Treatment of experimental chronic osteomyelitis caused by Morganella morganii with mezlocillin and cloxacillin.

Mezlocillin was used alone and in combination with cloxacillin in the treatment of chronic experimental osteomyelitis due to Morganella morganii. This combination showed in vitro synergy as measured by the checkerboard technique. A marked inoculum affect was demonstrated in vitro with mezlocillin and the infecting strain of M. morganii. In therapeutic trials, mezlocillin administered for 28 days was totally ineffective. The combination of mezlocillin and cloxacillin (at 800 and 400 mg/kg, respectively, 4 times a day) given for 28 days was significantly better than either no therapy or therapy with mezlocillin alone. However, even after 4 weeks of combined therapy with mezlocillin and cloxacillin M. morganii was recovered from the bones of 55% of the treated rabbits.

Stability of mezlocillin sodium as determined by high-performance liquid chromatography.

The stability of mezlocillin sodium solutions in water with either phosphate buffers or other ingredients used in intravenous admixtures (dextrose, fructose, and sodium chloride) has been studied using a stability-indicating high-performance liquid chromatographic method. This assay shows a relative standard deviation of 1.42% based on six injections. The optimum stability was shown at an approximate pH of 4.8, and solutions in dextrose (5%) and sodium chloride (0.9%) were stable for up to 4 days at 25 degrees, 36 days at 5 degrees, and for 60 days at -10 degrees. When refrigerated, the solutions in 5% fructose and 10% dextrose were as stable as those in 5% dextrose.

[Tissue concentrations of mezlocillin in prostate adenomas following intravenous bolus injections and continuous infusions]. / Gewebekonzentrationen von Mezlocillin im Prostataadenom nach intravenösen Bolusinjektionen und Dauerinfusionen.

In a total of 23 patients undergoing transurethral resection or suprapubic operation of benign hypertrophy of prostate perioperative antibiotic prophylaxis was started with 5 g of mezlocillin in each patient. In 5 patients (group I) the antibiotic was slowly (3 min) injected i.v. In 5 patients (group II) mezlocillin was administered as i.v. bolus injection of 1 g followed by i.v. infusion of 4 g during one hour. In 7 patients (group III) and in 6 patients (group IV) mezlocillin was administered as i.v. bolus injection of 1 g followed by i.v. infusion of 4 g during 4 hours. In the patients of group I-III a transurethral resection and in the patients of group IV a suprapubic prostatectomy was performed. Serum concentrations of mezlocillin were determined in intervals up to 4 hours after start of administration. The prostatic tissue concentrations were determined in both prostatic lobes in group I and group II 60 and 90 min and in group III and IV 4 hours after start of administration. In group V several tissue samples of the prostatic adenoma were obtained. The serum concentrations showed considerable interindividual variations, because the dose of antibiotic was the same in each patient and not adapted to the body weight. In group I the mean prostatic tissue concentrations at 60 min and 90 min after start of administration were 76 micrograms/g and 31 micrograms/g, respectively, in group II the mean prostatic tissue concentrations at 60 min and 90 min were 78 micrograms/g and 24 micrograms/g, respectively. In group III the mean tissue concentration at the end of the 4-hours infusion was 29 micrograms/g. In 2 patients of this group the concentrations of the 2 prostatic lobes differed considerably. In group IV measurable tissue concentrations of mezlocillin were found in 2 patients only. Considerable variations were found within the prostatic adenoma ranging from "non detectable" to approximately half of the serum concentration.(ABSTRACT TRUNCATED AT 250 WORDS)