Distribution of Labeled Antibiotics in Different Components of Milk Following Intramammary and Intramuscular Administrations

Gil, Ziv; Rasmussen, Folke

doi:10.3168/jds.s0022-0302(75)84660-1

Cited by 24 publications

(38 citation statements)

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“…In the in vivo study, amoxicillin accumulated more in skim milk, whereas tylosin persisted in cream. In studies conducted on dairy animals such as cows and goats, lipophilic drugs, including triclabendazole, closantel, chloramphenicol, and rafoxanide, accumulate more in cream, whereas hydrophilic drugs such as benzylpenicillin and levamisole accumulate more in skim milk (Ziv and Rasmussen, 1975;Power et al, 2012Power et al, , 2013a. We hypothesize that even though amoxicillin does not have a high binding degree to casein, the high accumulation ratio of amoxicillin in skim milk may be related to its hydrophilicity.…”

Section: Discussionmentioning

confidence: 87%

“…Casein was obtained using minor modifications of the method reported by Ziv and Rasmussen (1975) and Morton (1954). Casein was separated from skim milk (10 ± 0.1 g) following centrifugation at 4,000 × g for 45 min 3 times at 2°C.…”

Section: Separation Of Whole Milk To Milk Fractionsmentioning

confidence: 99%

“…Drugs can reside in one or more milk fractions bound to protein such as casein, dissolved within fat globules, or free in the aqueous medium (Craig and Stitzel, 2004). Drug distribution to the different fractions of milk varies according to both the route of administration and the dose (Ziv and Rasmussen, 1975;Power et al, 2013a). In particular, protein binding degree and lipophilicity play an important role in drug distribution in the milk (Agatonovic-Kustrin et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Distribution of hydrophilic and lipophilic antibacterial drugs in skim milk, cream, and casein

Özdemir

Traş

Üney

2018

Journal of Dairy Science

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This study determined the distribution of drugs to different milk fractions according to their physicochemical properties. Hydrophilic drugs tend to concentrate in skim milk, whereas lipophilic drugs tend to concentrate in cream. The concentration of a drug in casein is related to its degree of binding to milk proteins. Thus, we aimed to determine whether withdrawal time in whole milk differs from that in cream, casein, and skim milk. Amoxicillin and tylosin were selected as prototype hydrophilic and lipophilic drugs, respectively. The study was conducted in vitro and in vivo to determine whether in vitro conditions reflect the distribution of drugs in the different milk fractions in vivo. The in vivo study was conducted using a crossover design on 6 healthy Holstein dairy cattle. First, amoxicillin (i.m., single dose, 14 mg/kg) was administered to cows. Following a 1-wk washout period, tylosin (i.m., single dose, 15 mg/kg) was administered. Concentrations of amoxicillin and tylosin in milk and milk fractions were measured using HPLC-UV. In the in vitro study, 0.04 to 400 μg/g of amoxicillin and 0.05 to 50 μg/g of tylosin were spiked to drug-free milk and the concentrations in milk and milk fractions were measured. In addition, the percentage of total protein in milk and milk fractions was determined. Amoxicillin accumulated more in skim milk than in cream and casein, both in vitro (92%) and in vivo (73%, skim milk-to-whole milk ratio). The distribution of tylosin in whole and skim milk was similar to that of amoxicillin in the in vitro study, in contrast to the accumulation of tylosin in cream seen in vivo. However, the accumulation ratio of tylosin in cream was lower than expected. By either method, tylosin was less concentrated in casein than in skim milk and cream. The percentage of total protein was similar in skim milk and whole milk and higher than in cream. Thus, amoxicillin accumulates less in cream and casein, suggesting that these fractions would pose a lower risk to the consumer. Tylosin was still present at the maximum residue limit (50 μg/kg) 24 h after injection in the casein fraction and 48 h after injection in the cream fraction.

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Section: Discussionmentioning

confidence: 87%

Section: Separation Of Whole Milk To Milk Fractionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Distribution of hydrophilic and lipophilic antibacterial drugs in skim milk, cream, and casein

Özdemir

Traş

Üney

2018

Journal of Dairy Science

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“…The distribution volume of chloramphenicol in ruminants is large, i.e. approaching total body volume (7,11,12,13). Antibiotics with similar kinetic properties are expected to produce tissue drug concentrations/ serum drug concentration ratios close to unity (6).…”

Section: Resultsmentioning

confidence: 99%

Serum chloramphenicol levels and the intramuscular bioavailability of several parenteral formulations of chloramphenicol in ruminants

Nouws¹,

Gil²

1979

Veterinary Quarterly

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Summary Serum chloramphenicol concentrations were determined by microbiological and chemical assay methods in cows, ewes, and goats treated parenterally with seven different veterinary parenteral chloramphenicol products, including the water soluble sodium succinate ester of chloramphenicol and solutions of 20%, 25% and 50% of chloramphenicol base in various organic solvents. Serum drug concentrations were analyzed for the effect of product formulation differences, dosage, whether the drug was administered i.m. at a single body site or to two sites, and the method of assay, on the absorption from the injection site, peak drug levels, and the persistence in serum of effective concentrations of the drug i.e. 5 to 10 ug / ml. Although differences were observed among the 6 products containing chloramphenicol base in respect to absorption rate and peak serum drug levels, and although these differences significantly influenced the persistence of microbiologically-active serum drug concentrations at the level of ≥ 10 μg / ml, they did not at the level of ≥ 5 μg / ml. In the animal species examined, injections given at 2 sites appeared to influence the duration of predetermined serum drug levels more than the differences among the products in respect of the absorption and elimination rates from serum, the peak serum concentrations, and the dose. The shapes of the concentration-to-time curves in cows and ewes injected with the same dose of a given product were essentially the same, but they were different in goats. Serum chloramphenicol concentrations measured chemically after treatment with chloramphenicol base were 20% to 46% higher than those measured microbiologically. For 60 minutes after the sodium succinate ester had been administered i.v. and i.m. to ewes, the chemically determined chloramphenicol levels were more than twice as high as the respective concentrations determined by microbiological assay, but thereafter, the magnitude of those differences was not greater than observed after treatment with chloramphenicol base. Intramuscular bioavailability of the products containing chloramphenicol base injected at 2 sites was rather poor (51% to 80.5%ofthe dose) and even lower values were calculated after injection at a single site. Results are briefly discussed of the effect of dosage form on the persistence of microbiologically effective serum drug levels. A dose of at least 50 mg / kg to be administered i.m. at two sites are essential prerequisits for chloramphenicol therapy in ruminants.

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“…However, the activity of dihydrostreptomycin is markedly decreased in the presence of milk 61 , possibly owing to extensive binding to milk protein 71 . It is very unevenly distributed in the udder parenchyma, taking up to 8 hours to achieve wide distribution 63 , and is unlikely even at very high doses to reach therapeutic levels in milk 70 .…”

Section: Aminoglycosidesmentioning

confidence: 99%

Bovine mastitis therapy and why it fails : continuing education

Preez¹

2000

J. S. Afr. Vet. Assoc.

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Treatment of bovine mastitis depends on the cause, the clinical manifestation and the antibiotic susceptibility of the agent. Mastitis therapy is commonly unsuccessful owing to pathological changes that occur in the udder parenchyma as a result of the inflammatory reaction to mastitogenic bacteria, pharmacokinetic properties of antimicrobial mastitis drugs, mastitogenic bacterial and related factors, and poor animal husbandry and veterinary interventions.Key words: infectious bovine mastitis, mastitogenic bacterial factors, mastitis therapy, pathological udder changes, pharmacokinetic properties, poor animal husbandry. activity 2 . However, the blood circulation through the udder of a cow producing 20 kg of milk per day is approximately 10 000 /d, or 7-10 /min 22 . Systemic administration of rationally selected antibacterials can therefore be used as the sole treatment in acute mastitis. Following systemic administration, basic drugs (if sufficiently lipid-soluble) tend to concentrate in milk. The non-ionised fraction reaches equal concentrations on either side of the the blood-milk barrier 29 , even when marked udder changes are present.An ideal antibiotic for parenteral mastitis therapy should have a low MIC against the majority of udder pathogens, high bioavailability via the intramuscular route, sufficient lipid solubility, a low degree of serum protein binding, a long half-life in the body, similar clearance from organs, tissues and blood, no distribution to the gastrointestinal tract, and be weakly basic or otherwise highly nonionised in serum 40,49,67 . To date, as far as we know, no single antibiotic meets all these requirements.Therapy of acute mastitis should commence as soon as possible after diagnosis 12,58 , using a highly bioavailable antibiotic, with the necessary supportive therapy 41 . The milder the pathology in the udder parenchyma, the better the prognosis.The duration of treatment depends on the clinical symptoms, medical history of the cow and microbiological diagnosis. Lengthy treatment means a lengthy milk withdrawal period, which makes the treatment costly. If the cow has chronic mastitis that cannot be cured during lactation, culling is the obvious solution. However, sufficiently lengthy treatment of a cow with a good prognosis may lead, in addition to clinical recovery, to elimination of the bacteria from the udder.All cows that have had clinical mastitis during lactation should be given dryingoff therapy. SPECIFIC THERAPY FOR THE VARIOUS FORMS OF MASTITIS Teat canal infection (TCI)Treating lactating cows with small quantities of antibiotic (1 to 2 droplets) introduced 3 times at 12-hourly intervals effectively eliminates teat canal infection 9,10 . Teat canal therapy is not advocated commercially. A high percentage of TCI (> 50 %) undergo spontaneous recovery (self-cure) when predisposing factors to mastitis are limited or eliminated 9 . Subclinical mastitisFor treatment to make a significant contribution to reducing the incidence of mastitis, it is necessary to treat subclini...

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Distribution of Labeled Antibiotics in Different Components of Milk Following Intramammary and Intramuscular Administrations

Cited by 24 publications

References 3 publications

Distribution of hydrophilic and lipophilic antibacterial drugs in skim milk, cream, and casein

Distribution of hydrophilic and lipophilic antibacterial drugs in skim milk, cream, and casein

Serum chloramphenicol levels and the intramuscular bioavailability of several parenteral formulations of chloramphenicol in ruminants

Bovine mastitis therapy and why it fails : continuing education

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