Background: Rifaximin is a non-aminoglycoside antibiotic utilized for the treatment of mastitis in cows, but its milk disposition kinetics, residue, and bacteriological status in lactating cow milk have hardly been reported. This study aimed to assess the milk disposition kinetics and residue of rifaximin in milk and to evaluate the bacteriological status in milk after intramammary treatment with rifaximin. Methods: An ultra-high-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) approach was developed to assess rifaximin concentrations in milk. Milk disposition kinetics parameters of rifaximin in cow milk were obtained by non-compartment model analysis. Rifaximin residues in milk were analyzed up to 108 h post-administration to estimate the withdrawal period. Clinically, the efficacy of Rifaximin Intramammary Infusion (Lactating Cow) was evaluated in mastitis cases caused by various pathogens and compared with lincomycin as the control drug, including clinical cure rate, bacteriological cure rate, and somatic cell count (SCC) at D21 post-treatment. Results: The C_max of rifaximin in milk was 54,273.3 ± 12,421.32 ng/mL, the area under the curve (AUC) was 340,731.8 ± 43,968.82 h⋅ng/mL, the T_1/2 was 5.57 ± 0.68 h, the mean resident time (MRT) was 7.3927 ± 1.34 h, and the area under the moment curve (AUMC) was 2,475,745 ± 230,305.1 h⋅h⋅ng/mL. Based on rifaximin residues in milk, the withdrawal period for cow milk was calculated to be 95.1 h. Clinically, Rifaximin Intramammary Infusion (Lactating Cow) demonstrated a clinical cure rate of 83.33% and a bacteriological cure rate of 76.67% in mastitis cases caused by various pathogens, with both rates being 10% higher than those of lincomycin. At D21 post-treatment, the rifaximin group had a significantly lower SCC than the lincomycin group (p < 0.05). Conclusions: Rifaximin exhibits favorable milk disposition kinetics, an acceptable withdrawal period of 95.1 h, and good clinical and bacteriological cure rates in bovine mastitis. These findings support rifaximin as a useful intramammary option and contribute to rational antimicrobial use and milk safety in dairy.

The purpose of this study was to use data mining and network pharmacology to determine drug patterns for bovine viral diarrhea (BVD). The frequency, properties, tastes, meridian tropism, and functions of prescription data were gathered and examined from four literature databases (2004–2024). Cluster analysis was used to find prescription patterns, and the Apriori algorithm (SPSS Modeler 18) was used to find associations. A total of 391 literature-derived prescription records were included in the analysis, involving 189 distinct herbal medicines and a cumulative herb-use frequency of 2031 occurrences. These herbs primarily enter the liver meridian and were categorized as cold, warm, or neutral. The predominant tastes were bitter, pungent, and sweet. Five frequently recorded herbs and 14 co-occurrence patterns among herbs were extracted. According to traditional Chinese medicine (TCM), spleen–stomach deficiencies and damp-heat pathogens are linked to BVD. These medication patterns were mainly associated with heat-clearing, detoxification, spleen-strengthening, and Qi-regulating strategies in TCVM theory. Targets were screened, PPI networks were constructed, and enrichment studies for core herbs (Baitouweng, Huangbo, Huangqin, Qinpi, and Zhizi) were performed using network pharmacology. The binding affinities between disease targets and active components were further assessed using molecular docking. The findings provide a descriptive summary of medication patterns and generate preliminary hypotheses regarding potential compound–target–pathway associations involved in the symptomatic and supportive use of TCM for BVD.