Minimal inhibitory concentrations for canine isolates and oral absorption of roxythromycin in fed and fasted dogs.
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Administration, Oral↗
Biomedical subjects
G Ziv
Publications and source records attributed to G Ziv.
Pharmacokinetics, intramuscular bio-availability, and bioequivalence of amoxycillin in donkeys.
The disposition kinetics of intravenously (i.v.) administered amoxycillin sodium (10 mg/kg) was determined in four adult donkeys. The elimination half-life (t1/2 beta) of 47.3 +/- 5.1 min, the apparent volume of distribution (Varea) of 0.325 +/- 0.093 l/kg and the total body clearance (ClB) of 4.76 +/- 1.33 ml/min.kg were very close to the corresponding values reported for the horse injected i.v. with amoxycillin sodium. It was evident that because of the rapid rate of drug elimination, limited distribution volume, and high clearance values, the i.v. injected amoxycillin sodium (10-20 mg/kg) was likely to result in potentially therapeutic tissue concentrations for a short time (2-3 h) only. Three formulations of 15% amoxycillin trihydrate suspension in oil were injected intramuscularly (i.m.) to each donkey at 10 mg/kg. Drug absorption was rapid and the elimination half-life (t1/2el) ranged between 6 and 10 h. Mean peak serum amoxycillin concentrations (Cmax) were, however, rather low (0.81-1.68 micrograms/ml) and the i.m. bioavailability was 25.8-45.1% for the different formulations. Although the three formulations were considered to be intramuscularly bio-equivalent and appeared to be well tolerated, it was estimated that multiple SID (once daily) treatments at 10-20 mg/kg could result in tissue concentrations of potential therapeutic value for the treatment of infections caused by very susceptible pathogens only.
Amoxicillin↗
Clinical pharmacologic aspects of cefixime in dogs.
The minimal inhibitory concentration (MIC) of cefixime, a new third-generation orally administered caphalosporin, was determined for reference and clinical isolates from dogs. The MIC of the drug for all but 1 of the 18 Enterobacteriaceae isolates tested, 1 Pasteurella canis, 1 Rhodococcus equi, 1 Streptococcus canis, and 1 Streptococcus group G isolate, was less than 1.0 microgram/ml. The MIC for 9 Staphylococcus intermedius isolates ranged from 1.56 to 6.25 micrograms/ml and, for 8 Sta aureus isolates, the MIC values ranged from 1.56 to 12.5 micrograms/ml. Pseudomonas aeruginosa, Actinomyces sp, and a single Bordetella bronchiseptica isolate were considered resistant to cefixime. Cefixime was administered orally in 2 phases at a standard dosage of 5 mg/kg of body weight to clinically normal adult male and female dogs. In the first phase, the drug was given once as a capsule and once as a suspension. In the second phase, it was administered once per day for 6 consecutive days in capsule form. Serum drug concentration was determined by use of a microbiological assay, and the following kinetic values were estimated for each dog: area under the concentration-time curve, peak serum drug concentration (Cmax), time of Cmax, absorption half-life, and elimination half-life (t1/2el). The kinetic profile of the drug in serum after oral administration of a single dose of cefixime was similar, with mean Cmax values of 3.36 and 4.76 micrograms/ml after treatment with the capsule and suspension, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Norfloxacin nicotinate in the treatment of Pseudomonas aeruginosa infection in the genital tract of a bull.
Consecutively collected semen samples from a breeding bull were found to be contaminated with Pseudomonas aeruginosa. Palpation through the bull's scrotum revealed inflammatory changes suggestive of chronic orchiepididymitis in one testicle. For 10 months, all the bull's 13 ejaculates were discarded because the post-thaw viability was < 20%. Norfloxacin nicotinate was injected intramuscularly into the bull at 5 mg/kg daily for 7 days. Serum and semen samples were collected at 24-h intervals during the course of treatment and afterwards and were assayed for NFN concentrations. Drug concentrations in the semen, by microbiological assay, during treatment and up to 120 h after the last treatment ranged from 2.6 to 5.1 micrograms/ml, 14.2 to 43.2 times the corresponding serum drug levels. P. aeruginosa was not isolated from the semen 4 or 15 days after the last injection but was re-isolated after 32 and 64 days. A second similar course of NFN was administered and P. aeruginosa was not isolated from semen samples collected on four occasions, 6, 22, 44 and 94 days after the last treatment.
Animals↗
Lincomycin and spectinomycin in the treatment of breeding rams with semen contaminated with ureaplasmas.
Ureaplasma species were isolated from semen samples collected sequentially from one Awassi and three Assaf breeding rams. Each ram was injected subcutaneously with an aqueous solution of lincomycin and spectinomycin for five consecutive days at a dose equivalent to 4.5 mg kg-1 lincomycin and 9.0 mg kg-1 spectinomycin daily. Serum and semen samples were collected at intervals during the treatment and assayed for lincomycin. No Ureaplasma species were isolated from semen samples collected during the course of the treatment and at intervals for 17 days after the last treatment. The concentration of lincomycin in semen ranged from 0.51 microgram ml-1 four hours after treatment to 0.08 microgram ml-1 24 hours after treatment, and these levels were three to nine times higher than the corresponding serum concentrations.
Animals↗
Anti-inflammatory ketoprofen in the treatment of field cases of bovine mastitis.
The efficacy of ketoprofen in the treatment of acute clinical mastitis was evaluated in a clinical trial comprising a non-blind controlled study and a blind, placebo-controlled study. All the cows were treated with 20 g sulphadiazine and 4 g trimethoprim intramuscularly upon diagnosis, and half the dosage was given once daily thereafter. In addition, the ketoprofen treatment groups received 2 g ketoprofen intramuscularly once daily for the duration of the antimicrobial therapy. Recovery rates for the non-blind contemporary controls and the blind placebo-controls were 83.7 per cent and 70.7 per cent, respectively. In the non-blind controlled ketoprofen and the placebo-controlled ketoprofen treatment groups, recovery rates were 94.7 per cent and 92.3 per cent, respectively. The odds ratio (OR) of recovery was significantly (P < or = 0.01) high in the placebo-controlled study (OR = 6.75, confidence interval [CI] = 1.45 to 31.4), and high but not significant in the non-blind controlled study (OR = 2.64, CI = 0.53 to 13.10). It was concluded that ketoprofen significantly improved recovery in clinical mastitis in dairy cows.
Animals↗
Clinical pharmacokinetic characterization of norfloxacin nicotinate in swine following systemic administration.
Norfloxacin nicotinate (NFN) is a new water-soluble fluoroquinolone antibacterial agent. The in vitro activity of NFN for microorganisms isolated from swine and the pharmacokinetic properties of NFN following single intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administration were investigated. The minimal inhibitory concentrations (MIC's) of NFN for a wide range of reference (ATCC-American Type Culture Collection) microbial swine isolates, comprising 21 bacterial and 5 mycoplasmal species, ranged between 0.03 micrograms/ml (for Salmonella cholerasuis and Actinobacillus pleuropneumonia) and 12.5 micrograms/ml (for Streptococcus porcinus). The MIC of NFN for Mycoplasma hyopneumoniae, the causative agent of enzootic pneumonia of pigs, was < 1.0 microgram/ml although M. hyosynoviae was less sensitive, with a MIC value of 3.12 micrograms/ml. The MIC values of the drug for swine field isolates, comprising 8 bacterial species, were in good agreement with the values determined for the corresponding ATCC strains. Pharmacokinetic values for NFN were calculated following i. v. administration at 7.0 mg/kg and i. m. and s. c. administration at 14.0 mg/kg in a 3-way cross over study involving 6 pigs. Plasma concentrations of unchanged drug were determined by HPLC during 24 h post injection. Plasma NFN concentrations measured after i.v. dosing best fitted a 2-compartment open system pharmacokinetic model. The harmonic mean distribution half-life (t1/2 alpha) and elimination half-life (t1/2 beta) were 4.2 minutes and 2.1 h, respectively. The mean residence time (MRT) was 2.9 +/- 0.6 h and the steady state volume of distribution (Vss) was 3.2 +/- 0.1 l/kg. The mean t1/2 beta values after either i. m. or s. c. administration were 4.45 h with very rapid absorption rates (< 15 min to peak plasma drug concentration). Bioavailability was 51-64%. Less than 20% and 25% of the dose were excreted in the urine as parent drug during the first 24 h after i.v. and s.c. dosing, respectively whereas the amount of unchanged drug recovered in the feces was very small (1.3 to 1.6% of the dose). The pharmacokinetic and MIC data generated in the course of the present study suggest that a dose schedule of 14.0 mg/kg injected i. m. or s. c. every 24 h is capable of achieving and maintaining tissue drug concentrations of potential therapeutic value for the treatment of the most common bacterial and mycoplasmal infections in swine.
Absorption↗
Tissue distribution and binding to plasma proteins of norfloxacin nicotinate after intramuscular administration in pigs.
Three clinically normal pigs were given a single intramuscular injection of an aqueous solution of norfloxacin nicotinate (NFN) at 14 mg/kg body weight. Animals were killed 4 h after treatment and the concentrations of norfloxacin in various biological fluids and tissues were determined by chemical (high performance liquid chromatography, HPLC) and microbiological assay methods. Drug distribution throughout the body was presented as actual concentrations (micrograms/ml and ppm) in each sample and as the ratio of drug concentration in tissue to drug concentration in plasma. Highest concentrations were found in the urine, kidney, liver and bile. The drug was not detected in ocular fluid, brain tissue (by microbiological assay), fat (by HPLC) and skin (by HPLC). Tissue-to-plasma concentrations ratios were near to, or greater than, 1.0 (HPLC assay) for the kidney, liver, spleen, muscle, lung, adrenals, salivary glands, pleural and synovial fluid, and smaller than 1.0 for cerebrospinal fluid, brain tissue and lymph nodes. Agreement between the chemical and microbiological assay results was variable, depending on the type of tissue and biological fluid tested. Binding of norfloxacin to plasma proteins in pig is low (23%-29%). The distribution pattern of the drug in pig, laboratory animals and humans is very similar; it can be characterized as extensive, with tissue-to-serum ratios reaching 2:1 or more in certain non-excretory organs. These values may reflect intracellular concentrations of the drug.
Animals↗
Treatment of peracute and acute mastitis.
This article discusses the cause and pathophysiology of peracute and acute mastitis. The pharmaceutic and pharmacologic properties of potential therapeutic agents, the interaction between the cow and the drug, and some practical aspects of using these drugs are reviewed.
Acute Disease↗
Polymyxin B: pharmacokinetics of single doses given intravenously and intramuscularly to turkeys, and minimal inhibitory concentrations for Escherichia coli and Pasteurella multocida.
The 50% and 90% minimal inhibitory concentrations (MIC50 and MIC90) of polymyxin B for avian Escherichia coli and Pasteurella multocida isolates were determined by the agar plate dilution method. Polymyxin B at approximate MIC level in serum was bactericidal for E. coli in 2 to 4 hours. Aqueous polymyxin B sulfate was administered by a single bolus intravenous injection into turkeys at 10,000 IU/kg, and by a single bolus intramuscular injection at 5,000, 10,000 or 20,000 IU/kg. Effective serum drug concentrations after intramuscular injection (MIC50 levels or greater) were maintained for E. coli for 7.0 hr (10,000 IU/kg) and 11.5 hr (20,000 IU/kg), and for P. multocida for 3.0 hr (10,000 IU/kg) and 4.1 hr (20,000 IU/kg). Pharmacokinetic parameters were calculated by non-compartmental methods. Elimination time half-lives, mean residence time, clearance, and apparent volume of distribution at steady state (Vdss) were all much higher for i.m. injection of 20,000 IU/kg than for i.m. injection of 10,000 IU/kg. We postulate that there exists a minimal tissue-interaction threshold concentration (MTC) at which polymyxin B can enter previously unavailable compartments or bind to previously refractory tissue components. Bioavailability of polymyxin B injected i.m. was 0.904 for the 10,000 IU/kg dose and 0.675 for the 20,000 IU/kg dose. Dosage intervals necessary to produce minimal steady state concentrations (Cssmin) equal to the MIC were calculated. Certain aspects of the use of the parameter Vdss, and limitations on the use of dosage interval calculations for polymyxin B, are discussed. One week after i.m. injection of polymyxin B at 10,000 IU/kg, high tissue drug levels were present, especially in bound form in liver. Following single injections, no toxic effects on turkeys were observed.
Animals↗
Pharmacologic enhancement or suppression of phagocytosis by bovine neutrophils.
Sixty-three drugs, belonging to 10 chemical classes, were tested in vitro to determine effects on phagocytosis of 32P-labeled Staphylococcus aureus by neutrophils isolated from milk. Within each class, the number of antibiotics tested were: nonsteroidal anti-inflammatory drugs (NSAID; 8), peptolids (2), aminoglycosides (8), tetracyclines and fusidic acid (4), beta-lactam antibiotics (25), secretolytic agents (2), macrolides (5), polypeptides (2), and antibacterial quinolones (8). Percentage of phagocytosis was determined after incubating (2 hours at 37 C) 12.5 x 10(6) viable neutrophils, 200 x 10(6) 32P-labeled S aureus with antibiotics and 5% skimmed milk. Concentrations of antibiotics tested were 1,000, 500, and 10 micrograms/ml of incubation media. When compared with nonantibiotic controls at the highest drug concentration, the NSAID acetylsalicylic acid and centrophenoxine increased phagocytosis 23.2 and 8.8%, respectively, and benzydamine, indomethacin, phenylbutazone, ibuprofen, and acetominophen decreased phagocytosis 22.8, 14.2, 9.8, 27.0, and 18.2%, respectively. The peptolids novobiocin and pristinamycin decreased phagocytosis 24.5 and 22.0%, respectively. The aminoglycosides tobramycin, amikacin, and gentamicin decreased phagocytosis 21.1, 15.4, and 19.2%, respectively. For the tetracyclines and fusidic acid, minocycline and doxycycline decreased phagocytosis 39.8 and 54.2%, respectively. The beta-lactam antibiotics carfecillin, cephapirin sodium, and cephacetrile sodium decreased phagocytosis 11.2, 12.8, and 23.8%, respectively. The secretolytic agent, bromhexin, increased phagocytosis 10.8%. These data indicate that the potential for enhanced phagocytosis exists through use of some NSAID, and for depressed phagocytosis through use of aminoglycosides, peptolids, tetracyclines, and beta-lactams, as well as certain other NSAID.
Animals↗
Systemic dry cow therapy--a preliminary report.
Efficacy of three different treatment regimens in the elimination and prevention of Staphylococcus aureus intramammary infection was studied in 106 dry cow periods. At drying off, norfloxacin nicotinate was given subcutaneously to 44 cows at 10 mg/kg, oxytetracycline-HCl was administered intramuscularly to 18 cows at 20 mg/kg, 500 mg cephapirin benzathine were infused into each udder quarter of 21 cows, and a group of 23 cows served as an untreated control. Number of existing Staphylococcus aureus intramammary infections was reduced only in the norfloxacin nicotinate treatment group. New infection rate appeared lower in the two systemic treatment groups. The percentage of infected quarters remained the same throughout the dry period in the norfloxacin treatment group but number of infected quarters increased by 33 to 85% (significant in the cephapirin group) in the other groups. Minimal inhibitory concentration of the drugs for 57 S. aureus isolates was determined. Isolates were sensitive to norfloxacin and cephapirin and moderately sensitive to oxytetracycline. Results suggest that systemic dry cow therapy using norfloxacin nicotinate, which possesses large distribution volume, long half-life, and is highly active against the pathogen involved, was more effective than the other treatments.
Animals↗
Effects of florfenicol, chloramphenicol, and thiamphenicol on phagocytosis, chemiluminescence, and morphology of bovine polymorphonuclear neutrophil leukocytes.
Florfenicol, chloramphenicol, and thiamphenicol were tested in vitro to determine their potential toxic effects on bovine neutrophils. Antibiotics were tested at 4000, 2000, and 10 micrograms/ml of incubation mixture. Percentage phagocytosis was determined by incubations with neutrophils isolated from milk of five cows and 32P-labeled Staphylococcus aureus and 5% skim milk. The effect of 4000 micrograms of each antibiotic on chemiluminescence was determined on neutrophils isolated from mammary secretions of three nulliparous heifers. Morphological evaluation by transmission and scanning electron microscopy was performed on neutrophils isolated from two heifers at antibiotic concentrations of 4000 and 10 micrograms/ml. Chloramphenicol depressed phagocytosis at the high and medium doses and blocked chemiluminescence activity at the high dose. No effects were observed for florfenicol and thiamphenicol. Transmission electron microscopic examination showed that at the high concentration of drugs, 99, 99, 97, and 76% of the neutrophils treated with florfenicol, chloramphenicol, thiamphenicol, and dimethyl sulfoxide were abnormal. Examination by scanning electron microscopy showed that the percentage of neutrophils without pseudopodia averaged 67, 94, 32, and 16%, respectively. Results indicated that neither florfenicol nor thiamphenicol altered neutrophil function, but they did alter neutrophil morphology, although to a lesser extent than did chloramphenicol.
Animals↗
In vivo effects of chloramphenicol, tetracycline, and gentamicin on bovine neutrophil function and morphologic features.
Antibiotics that have been shown in vitro to have a detrimental effect on bovine polymorphonuclear leukocytes (PMNL) were injected into the mammary gland. Chloramphenicol, tetracycline, gentamicin, or phosphate-buffered saline solution (PBSS) were administered to uninfected mammary quarters of four cows at recommended doses. Each cow received each of the 4 treatments. Total milk somatic cell count and N-acetyl-beta-D-glucosaminidase activity in milk in response to drug, changes in ultrastructure of PMNL, and effects on in vitro percentage phagocytosis, reduction of nitroblue tetrazolium, and chemiluminescence were studied. Chloramphenicol and tetracycline caused a significant (P less than 0.01) increase in somatic cell count, compared with baseline values. During the first 12 hours, no effect on NAGase activity was observed. All 3 antibiotics caused a significant (P less than 0.05) alteration of PMNL morphologic features. More abnormal PMNL (63%) were found in tetracycline-injected quarters. Gentamicin-injected quarters contained 33% abnormal PMNL, compared with only 5% for PBSS-injected quarters. A significant (P less than 0.01) decrease in percentage phagocytosis was observed for tetracycline and gentamicin. Tetracycline inhibited all chemiluminescence activity, whereas no effect was observed for the other 2 drugs. Nitroblue tetrazolium reduction was nonsignificantly (P greater than or equal to 0.05) decreased for the 3 drugs, compared with that for PBSS controls. On the basis of our findings, we concluded that some antibiotics may be inhibitory to phagocyte function and, thereby, impair host defense mechanisms against invading microbes.
Animals↗
Probenecid effect on cefuroxime pharmacokinetics in calves.
Cefuroxime pharmacokinetics were studied in unweaned calves. The antibiotic was administered at 10 mg/kg to six calves i.v., to 12 calves i.m. and to ten of the previous 12 calves i.m. at 10 mg/kg together with probenecid at 40 mg/kg. Intramuscular doses of cefuroxime alone at 20 mg/kg were given to seven calves; to five of these calves cefuroxime was also given together with probenecid at 40 mg/kg and at 80 mg/kg. The serum concentration-time data were analyzed using statistical moment theory (SMT). The elimination half-life (t1/2) was 69.2 min (harmonic mean) after i.v. and 64.8 min and 64.9 min following i.m. administration of the lower and higher dose, respectively. Co-administration of probenecid did not affect the t1/2. The mean residence time (MRT) was 80.9 +/- 23.5 min (mean +/- SD) after i.v. and 117.8 +/- 9.3 min and 117.7 +/- 5.4 min after i.m. administration of cefuroxime at 10 and 20 mg/kg, respectively. The MRTi.m. following administration of cefuroxime at 10 mg/kg together with probenecid at 40 mg/kg was 140.0 +/- 8.8 min. The MRTi.m. values were 132.8 +/- 2.3 min and 150.8 +/- 5.1 min after cefuroxime was given at 20 mg/kg together with probenecid at 40 mg/kg or 80 mg/kg, respectively. The total body clearance (ClT) was 3.56 +/- 1.11 ml/min/kg and the volume of distribution at steady state (Vd(ss] 0.270 +/- 0.051 l/kg. The MIC90 values of cefuroxime were 16 micrograms/ml for E. coli and Salmonella isolates, 0.5 microgram/ml for Pasteurella multocida and 2.0 micrograms/ml for P. haemolytica.
Animals↗
Pharmacokinetics of ceftazidime given alone and combination with probenecid to unweaned calves.
Ceftazidime pharmacokinetic values were studied in unweaned calves given the antibiotic alone or in combination with probenecid. Ceftazidime was administered IV to 9 calves at a dosage of 10 mg/kg of body weight and IM (10 mg/kg) to 8 calves, to 7 calves (10 mg/kg plus probenecid [40 mg/kg]), and to 9 calves (10 mg/kg plus probenecid [80 mg/kg]). Serum concentration-vs-time data were analyzed, using noncompartmental methods based on statistical moment theory. The data for IV ceftazidime administration also were fitted by use of a linear, open 2-compartment model. The mean (+/- SD) terminal half-life was 138.7 +/- 23.6 minutes and 126.3 +/- 10.5 minutes after IV and IM administrations, respectively. The mean residence time was 167.3 +/- 21.1 minutes and 201.4 +/- 16.8 minutes after IV and IM administrations, respectively. Coadministeration of probenecid did not affect the terminal half-life or mean residence time values. The total body clearance was 1.75 +/- 0.26 ml/min/kg, and the volume of distribution at steady state was 0.294 +/- 0.064 L/kg. The estimated mean absorption time was 34.1 minutes. There were no significant differences between the mean residence time calculated by statistical moment theory or by compartmental analysis, indicating central compartment output of ceftazidime. The 90% minimal inhibitory concentration values of ceftazidime determined for Escherichia coli, Salmonella spp, Pasteurella multocida, and P haemolytica isolates ranged from less than 0.01 to 0.1 micrograms/ml.
Animals↗
Pharmacokinetics of single doses of cefoperazone given by the intravenous and intramuscular routes to unweaned calves.
Cefoperazone pharmacokinetics were studied in unweaned calves. The antibiotic was administered to 10 calves intravenously, to eight calves intramuscularly at 20 mg kg-1 and to 10 calves intramuscularly at 20 mg kg-1 together with probenecid at 40 mg kg-1. Serum concentration versus time data were analysed by non-compartmental methods based on the statistical moment theory. The intravenous data were also fitted by a linear, open two-compartment model. The terminal halflife of cefoperazone was 127.9 +/- 28.2 min (mean +/- SD) after intravenous and 136.9 +/- 19.6 min after intramuscular administration. The t1/2 was increased to 257.3 +/- 127.3 min by the co-administration of probenecid. The total body clearance was 8.16 +/- 1.60 ml min-1 kg-1 and the volume of distribution at steady state was 0.713 +/- 0.167 litre kg-1. The mean residence time values were 87.2 +/- 10.6 min after intravenous and 140.3 +/- 20.6 min after intramuscular injection and were increased to 264.5 +/- 99.8 min by the co-administration of probenecid. The estimated mean absorption time was 53.1 min and the estimated bioavailability after intramuscular administration was 76.3 per cent. The minimal inhibitory concentration (MIC90) values of cefoperazone ranged from 0.5 to 2 micrograms ml-1 for Escherichia coli, salmonella groups C, D and E and Pasteurella multocida isolates. Salmonella group B strains appeared to be highly resistant to cefoperazone with MIC90 greater than 32 micrograms ml-1. There were no significant differences between the pharmacokinetic variables calculated by statistical moment theory or compartmental analysis indicating central compartment output of cefoperazone.(ABSTRACT TRUNCATED AT 250 WORDS)
Absorption↗
Pharmacokinetics of cephalexin glycinate in lactating cows and ewes.
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Animals↗