Fate of ivermectin residues in ewes' milk and derived products

The fate of ivermectin (IVM) residues was studied throughout the processing of daily bulk milk from 30 ewes (taken up to 33 d following subcutaneous administration of 0·2 mg IVM/kg b.w.) in the following milk products: yoghurt made from raw and pasteurized milk; cheese after pressing; 30- and 60-day ripened cheese; and whey, secondary whey and whey proteins obtained after cheese–making (albumin cheese). The concentration of the H2B1a component of IVM was analysed in these dairy products using an HPLC method with fluorescence detection. The mean recovery of the method was, depending on the matrix, between 87 and 100%. Limits of detection in the order of only 0·1 µg H2B1a/kg of product were achieved. Maximum concentrations of IVM were detected mostly at 2 d after drug administration to the ewes. The highest concentration of IVM was found on day 2 in 60-day ripened cheese (96 µg H2B1a/kg cheese). Secondary whey was the matrix with the lowest concentration of IVM

The Effect of Azithromycin on Ivermectin Pharmacokinetics—A Population Pharmacokinetic Model Analysis

This paper describes the use of a modeling and simulation approach to explore a reported pharmacokinetic interaction between two drugs (ivermectin and azithromycin), which along with albendazole, are being developed for combination use in neglected tropical diseases. This approach is complementary to more traditional pharmacokinetic and safety studies that need to be conducted to support combined use of different health interventions. A mathematical model of ivermectin pharmacokinetics was created and used to simulate multiple trials, and the probability of certain outcomes (very high peak blood ivermectin levels when given in combination) was determined. All simulated peak blood levels were within ranges known to be safe and well tolerated. Additional field studies are needed to confirm these findings

Thermal and long-term freezing stability of ivermectin residues in sheep milk

The stability of ivermectin residues in sheep milk under conditions of pasteurization (74 °C, 40 s), high pasteurization (80 °C, 1 min), and boiling (100 °C, 10 s) based on residue content (at a level of concentration of about 2 ?g/kg and 30 ?g/kg of H2B1a) and sort of ingestion (in vitro, in vivo) was studied. None of these factors influenced concentrations of ivermectin in the matrix investigated. Residues of ivermectin were also stable in milk after one year of freezing at -20 °C. After two years of freezing they had diminished by approximately one quarter. The concentration of the H2B1a component was analyzed using a combined HPLC method with fluorescence detection. Samples were extracted with acetonitrile and cleaned-up using a solid phase extraction on C8 minicolumns. Eluate was concentrated under stream of nitrogen and dry extracts were pre-column derivatized with trifluoroacetic anhydride and N-methylimidazole. The method used was extensively validate

Ivermectin pharmacokinetics in lactating sheep

Ivermectin (IVM) concentrations in plasma and milk were studied in six Istrian Pramenka dairy sheep after a single subcutaneous dose of 0.2 mg/kg b.w. of IVM in the early lactation period to describe IVM disposition in milk and to evaluate the transfer of IVM residues via milk to suckling lambs. Large inter-animal in concentration variability of IVM in both matrices was observed. The highest overall concentration was found in the same animal: 21.7 ¿g/l of H2B1a in plasma on the second day and 44.9 ¿g/kg of H2B1a in milk on the first day after the drug was administered. The mean time in which IVM concentrations fell below the limit of detection for the whole ewe group was 22 and 23 days for plasma and milk, respectively. Time course of IVM concentration in milk was following the time course of IVM concentration in plasma, with an overall mean±S.D. of milk/plasma ratio of 1.67±0.50 for the first 7 days of the experiment. A mean of 0.7% of the dose was excreted through milk. Individual pharmacokinetic parameters were determined by fitting a one-compartment model to the milk and plasma concentration¿time profiles. Mean tmax, cmax, t1/2ke and AUC values for plasma data were: 1.70±0.65 days, 11.88±6.96 ¿g/l, 2.85±1.97 days and 63.99±28.34 ¿gday/l, respectively, and for milk: 1.28±1.07 days, 22.67±18.27 ¿g/l , 3.56±2.01 days and 114.60±60.41 ¿gday/l, respectively. The highest level of concentration in suckling lamb plasma, 0.36 ¿g/l of H2B1a, was slightly above the limit of determination. The mean lamb to ewe ratio of areas under the plasma concentration¿time curve for the first 5 days was 0.02. On the basis of obtained results, it can therefore be claimed that indirect IVM exposure of the suckling lambs via milk was negligibl

Time profile of abamectin and doramectin excretion and degradation in sheep faeces.

We studied abamectin and doramectin excretion and their degradation in sheep faeces under field conditions on pasture after a single subcutaneous dose (0.2 mg/kg body weight). In the excretion experiment, maximal abamectin concentration (1277 ng/g dry faeces) was detected on day 3, while doramectin concentration showed two peaks (2186 and 1780 ng/g dry faeces on days 2 and 5, respectively). Both avermectins were excreted at approximately the same rate (k = 0.23 da