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

Abstract

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.

Emerging Electrochemical Sensors for Real-Time Detection of Tetracyclines in Milk

“…Generally, tetracyclines are lipophilic antibiotics, with the exception of oxytetracycline and chlortetracycline. A study proves that lipophilic tetracyclines tend to concentrate in the fatty fractions on milk rather than in aqueous such as skimmed milk [32]. Fat percentage in milk varies between cows on a farm.…”

“…Depending on their solubility properties, antibiotic molecules are not distributed evenly through the milk and essentially are binding to different fractions [32,35]. Hydrophilic antibiotics (such as some β-lactams, sulphonamides and fluoroquinolones) would concentrate in skim milk due to the absence of fat; hence, lipophilic drugs (such as some macrolides, e.g., tylosin) would tend to concentrate in, for instance, cream.…”

“…In fact, not only lipophilicity but also protein-binding properties play a significant role in antibiotic concentration distribution in milk. Some antimicrobial drugs (such as tylosin) tend to concentrate in casein protein fraction, for example [32]. In terms of tetracyclines, their protein-binding properties vary, with doxycycline having the highest range of 82-93%.…”

Determination of five antimicrobial families in droppings of therapeutically treated broiler chicken by high-performance liquid chromatography-tandem mass spectrometry

“…However, at 22 d post-treatment, it was only possible to detect TYL residues in one of the samples below the LOQ (32 µg kg −1 ), which was registered as not detected. Fluctuations in TYL concentrations during d 14 and 18 posttreatment ( Table 3 ) could be related with the metabolism and recirculation of this antimicrobial from other tissues of the bird, such as liver or fat, because like OTC, TYL is a lipophilic antibiotic ( Ozdemir et al, 2018 ).…”

Curative Effect Observation of Applying Silver-Zinc Bacteriostatic Cream to Patients with Second-Degree Burn under Targeted Nursing Intervention and Its Effect on Wound Healing Rate

“…The inclusion criteria for patients were as follows. The clinical diagnosis criteria for second-degree burn were met [ 7 ]. The patients were 18–45 years old.…”