Pharmacokinetics, oral bioavailability and tissue distribution of azithromycin in cats.

Azithromycin is the first of a class of antibiotics classified as azalides. In an initial experiment four cats were given a single dose of azithromycin 5 mg/kg orally (p.o.), followed 2 weeks later by a single intravenous bolus (i.v.) dose of 5 mg/kg. Subsequently, six cats were given [14C]azithromycin p.o. in a single dose of 5.4 mg/kg for the study of tissue distribution and metabolism. In both experiments, serial blood samples were collected and the plasma assayed for unchanged azithromycin to determine various pharmacokinetic parameters. After p.o. administration, bioavailability was 58% and absorption rapid with a tmax of 0.85 +/- 0.72 h and a Cmax of 0.97 +/- 0.65 microgram/mL. The harmonic mean terminal t1/2 after i.v. administration was 35 h. Tissue half-lives varied from 13 h in fat to 72 h in cardiac muscle. Three metabolites were identified in bile. Unchanged azithromycin accounted for 100% of the total radioactivity in lung and skin tissues when assayed. In comparison with other species, the bioavailability in cats is higher than in humans but lower than in dogs. As in the dog, > 50% of the azithromycin-related material in feline bile was unchanged azithromycin.

Determination of semduramicin sodium in poultry liver by liquid chromatography with vanillin postcolumn derivatization.

A liquid chromatographic (LC) method is described for the quantitative determination of semduramicin sodium in broiler liver when administered under projected use conditions. For this procedure, semduramicin sodium is extracted from liver with methanolic ammonium hydroxide, separated and concentrated by solid-phase extraction steps, and determined by LC with postcolumn derivatization with vanillin. The mean recovery of drug was 95% over the 40-320 ng/g range, the coefficient of variation was +/- 10% or better, and no interference was observed from commercial polyether ionophores. The minimum level of detection for semduramicin sodium in broiler liver is 25 ng/g.

Confirmation of danofloxacin residues in chicken and cattle liver by microbore high-performance liquid chromatography electrospray ionization tandem mass spectrometry.

A specific assay is described for the confirmatory identification of danofloxacin residues in edible tissues of cattle and chicken. The assay utilizes on-line microbore high-performance liquid chromatography and pneumatically assisted electrospray tandem mass spectrometry (MS/MS). Collision-induced dissociation of the danofloxacin protonated molecule results in two significant daughter ions. Monitoring both ions provides the specificity required for this confirmatory assay. Optimum electrospray and MS/MS operating conditions permitted the specific monitoring of danofloxacin and the confirmation of its residues in chicken and cattle liver extracts down to 50 ppb. The analysis of control liver or the commercially available antibacterial quinolones enrofloxacin and its metabolite ciprofloxacin gave no response under the assay conditions. The ratios of the two daughter ions were similar for danofloxacin standard solutions, fortified tissues and incurred tissues.

Electrospray ionization mass spectrometry of semduramicin and other polyether ionophores.

Pneumatically assisted electrospray mass spectrometry of polyether ionophores yields several molecular ions. A single metal adduct molecular ion can be obtained by the addition of a neutral salt to the HPLC mobile phase. This approach may be useful in structural studies of unknown ionophores and in the development of specific methods for their analysis in complex matrices. Collision-induced dissociation of the molecular ions provides additional structural information and enhanced specificity for trace analysis. HPLC mobile-phase composition and flow rates have been optimized for on-line analysis. Best response and lowest background noise were obtained at the flow rate of 40 microL/min of a mobile phase containing a 20/80 mixture of water and acetonitrile. The development of a specific confirmatory assay for the new ionophore semduramicin in chicken liver demonstrates the usefulness of on-line HPLC pneumatically assisted electrospray mass spectrometry.

High-performance liquid chromatographic quantitation of trimethoprim, sulfamethoxazole, and N4-acetylsulfamethoxazole in body fluids.

We describe a rapid, precise and simple procedure for the quantitative determination of trimethoprim, sulfamethoxazole, and N4-acetylsulfamethoxazole in body fluids by reversed-phase high-performance liquid chromatography. This method utilizes antipyrine as an internal standard with the compounds detected by dual-wavelength monitoring at 225 nm and 254 nm after a single-step extraction. Precision, sensitivity, and accuracy of this assay are within the range of clinical utility; the coefficient of variation is less than or equal to 3%, sensitivity less than 0.5 micrograms/ml for all compounds, and recovery greater than 97%. The short time for performance and small sample size makes the assay ideal for clinical drug monitoring and pharmacokinetic studies.

Pharmacokinetics of intravenous trimethoprim-sulfamethoxazole in children and adults with normal and impaired renal function.

Thirty-seven children and adults aged 0.2-82 years were treated intravenously with 150 mg of trimethoprim (TMP) and 750 mg of sulfamethoxazole (SMZ)/m2 every 8 hr, usually for known or suspected pneumocystis pneumonia; when necessary dosage was adjusted to maintain peak TMP levels of 5-10 micrograms/ml. On day 2 of treatment, mean peak levels of TMP-SMZ were 7.02 and 148 micrograms/ml, respectively, and mean half-lives were 9.6 and 10.7 hr, respectively. All age groups achieved similar peak levels of TMP-SMZ, although dosages per weight were higher in children than in adults. Peak increments (peak levels minus levels before infusion) were higher and more reliable after iv than after oral dosage (P less than 0.001). The half-lives of TMP and SMZ increased with age (r = +0.73 and +0.39, respectively) and were correlated directly with the level of serum creatinine (r = +0.85 and +0.39, respectively). Serum concentrations of N4-acetyl-SMZ, the major hepatic metabolite of SMZ, increased in proportion to concentrations of creatinine in serum (r = +0.92; P less than 0.001). Adverse effects included fluid overload due to the large dilution volume and thrombocytopenia, which was associated with higher serum TMP levels and longer treatment as compared with nonthrombocytopenic patients. A loading dose of 250 mg of TMP and 1,250 mg of SMZ/m2 is recommended, followed by maintenance doses of 150 mg of TMP and 750 mg of SMZ/m2 every 8 hr for children aged 10 years or younger and every 12 hr for adults with normal renal function. In renal failure the dosage interval (hr) should be increased to 12 times the serum creatinine level (mg/dl) (maximum, 48 hr). Serum concentrations of TMP and perhaps of N4-acetyl-SMZ should be monitored in patients with severe renal failure.