International Conference on Raw Materials To Processed Foods, Antalya, Türkiye, 11 - 13 Nisan 2018, ss.47
The physicochemical properties of drugs influence the behavior of drugs in the body and biological fluids such as the milk. Lipophilic drugs tend to concentrate in cream of the milk while hydrophilic drugs tend to concentrate in skimmed milk. It is predicted that depending on the physicochemical properties of the drugs used accumulate at different concentration in separate parts of the milk. Thus, we aimed to show whether the withdrawal time of total milk differ from cream and skimmed milk. The study was also conducted in vitro to establish the relationship between in vivo and in vitro studies. It is aimed that the data obtained from this study is a guide for future studies. This study also may contribute to the development of a new method that will improve the using of the milk of drug administered animals. In this study, amoxicillin and tylosin were selected as prototype of hydrophilic and lipophilic drugs, respectively. The study was conducted in two steps as in vitro and in vivo. In vivo study was performed in crossover design. In the study, healthy six Holstein breed cows supplied from private management which make intensive breeding were used as animal material. Firstly amoxicillin (IM, single dose, 14 mg/kg) was administered to cows. Milk samples were collected on day 0 (control) before drug administration and at 1, 3, 6, 9, 12, 24, 48, 72, 96, 120 and 144 hours after drug administration. Following washout period tylosin (IM, single dose, 15 mg/kg) was administered to each cow. Milk samples were collected on day 0 (control) before drug administration and at 24, 48, 72, 96, 120 and 144 hours after drug administration. Concentrations of amoxicillin and tylosin in whole milk, skimmed milk and cream were measured by HPLC-UV. The in vitro stage of the study, 0.004, 4 and 400 μg/mL concentration of amoxicillin and 0.05, 0.5 and 5 μg/mL concentration of tylosin were added to the drug free milk and drug concentrations in the whole milk, skim milk and cream were measured after incubation at 37 °C for 30 min. It was determined that amoxicillin is more accumulated in the skimmed milk than the cream in both in vitro and in vivo stages of the study. Tylosin concentrations in whole milk and skimmed milk were similar the in vitro studies while the results of the in vivo studies showed that tylosin more accumulated in the cream more than the skimmed milk. But the rate of transition of tylosin to cream was less than expected. As a result, it can be stated that amoxicillin with the hydrophilic accumulate less in the cream and therefore the legal washout period of amoxicillin in the cream may be shorter than the whole milk. But, there is needed for additional work with more sensitive analysis methods to verify this prediction. The concentration of tylosin in the cream was less than predicted. This may be due to the zwitterion property besides the lipophilicity of the tylosin.