The dose regimen formulation of doxycycline hydrochloride and florfenicol injection based on ex vivo pharmacokinetic-pharmacodynamic modeling against the Actinobacillus pleuropneumoniae in pigs

Doxycycline hydrochloride and florfenicol combination(DoxHcl&FF)is an effective treatment for respiratory diseases.In the study,our objective Was to evaluate the activity of DoxHcl&FF against Actinobacillus pleuropneumoniae(APP)in porcine pulmonary epithelial lining fluid(PELF)and the optimal dosage scheme to avoid the development of resistance.The DoxHcl&FF Was administered intramuscularly(IM)at 20mg/kg,and the PELF was collected at differ-ent time points.The minimum inhibitory concentration(MIC)and time-mortality curves were also included in the study.Based on the sigmoid Emax equation and dose equations,the study integrated the in vivo pharmacokinetic data of infected pigs and ex vivo pharmacodynamic data to obtain the area under concentration time curve(AUCo-24h)MIC values in PELF and achieve bacteriostatic activity,bactericidal activity and the virtual eradication of bacteria.The study showed that the combination of DoxHcl and FF caused no significant changes in PK parameters.The peak concentration(Cmax)of FF in healthy and diseased pigs was 8.87±0.08 and 8.67±0.07μg/mL,the_AUCo-24h were.172.75±2.52 and 18022±3.13 h-μg/mL,the Cmax of DoxHcl was 7.91±0.09 and 7.99±0.05μg/mL,and the AUCo-24h was 129.96±3.70 h-μg/mL and 169.82±4.38 h-μg/mL.DoxHcl&FF showed strong concentra-tion-dependent tendencies.The bacteriostatic,bactericidal,and elimination activity were calculated as 5.61,18.83 and 32.68 h,and the doses were 1.37(bacteriostatic),4.59(bactericidal)and 7.99(elimination)mg/kg.These findings indicated that the calculated recommended dose could assist in achieving more precise administration,increasing the effectiveness of DoxHcl&FF treatment for APP infections.

Determination of Doxycycline in Doxycycline Hydrochloride Soluble Powder under Different Chromatographic Conditions

[Objectives]This study was conducted to compare the accuracy and detection speed of high performance liquid chromatography for determining the content of doxycycline hydrochloride in doxycycline hydrochloride soluble powder under different chromatographic conditions, in order to improve the level of laboratory testing. [Methods] Four sets of experiments were designed through a cross-test method. The contents of doxycycline hydrochloride in the raw materials of doxycycline hydrochloride and doxycycline hydrochloride soluble powder were determined by changing the chromatographic column and mobile phase conditions, and the feasibility and practicability of the four methods were judged by comparing the detection results through data and chromatographic signal processing. [Results] The content of doxycycline hydrochloride in finished doxycycline hydrochloride soluble powder and the raw materials of doxycycline hydrochloride could be accurately determined under the four chromatographic conditions, of which the experimental group using Agilent C18 column and the mobile chromatography conditions of finished doxycycline hydrochloride soluble powder had the shortest retention time. [Conclusions] The high performance liquid chromatography method using Agilent C18 chromatographic column and mobile phase chromatographic conditions of finished doxycycline hydrochloride soluble powder products can quickly and accurately determine the content of doxycycline hydrochloride in doxycycline hydrochloride soluble powder.