Studies Of Pharmacokinetics And Residues Of Doxycycline Hydrochloride Soluble Powder In Pigs

In China, Intensive, large-scale farming has developed rapidly. But the density ofbreeding also made bacteria spread rapidly and large-scale which has brought the hugeeconomic loss for the animal husbandry. Doxycycline was a broad-spectrum antibacterialagent of the tetracyclines family, which had similar antimicrobial spectrum with tetracyclineantibiotics, but it's antibacterial activity was better than the tetracycline for 2-4 times, and itwas powerful, and long-term, no significant nephrotoxicity. The study of pharmacokineticsand residues of doxycycline hydrochloride in pigs will determine the pharmacokineticparameters and withdrawl periods (WDT) to guide clinical treatment.This research has established the method of detection doxycycline (DOX) afterextraction from the plasma and tissue of pigs, using reversed-phase high performance liquidchromatography (RP-HPLC). The plasma and tissues samples were collected at differentintervals after adiministation of DOX. The blood samples were determined by usingRP-HPLC after liquid-liquid extraction and the tissue sample were determined by usingRP-HPLC after solid-phase extraction. The concentration-time data of DOX in plasma wereanalyzed with 3P97 computer program and WDT was determined by simple decision making.The correlation of calibration curve were all good, which correlation coefficient were morethan 0.9990. The limits of detection (LOD) was 0.075μg/mL,0.010μg/g,0.010μg/g,0.020μg/g,0.020μg/g in plasma,muscle,skin,liver,kidney, respectively. The averageextraction recovery was more than 69% from the tissues and plasma. The intra-daycoefficient of variations and inter-day coefficient of variations were less than 10%, 15%respectively.The pigs received single oral dose of DOX (5mg/kg b.w.) and samples of blood werecollected at different time. The result indicated the plasma drug concentration-time data werefitted two-compartment open models. The absorption rate constant (K_a) of DOX was found tobe 0.25±0.02h^-1, whereas the elimination half-life (t_1/2β) of the drug was 6.02±0.83h. The areaunder the serum concentration-time curve (AUC) was 17.07±2.80μgmL^-1h. The distributionvolume (V_d/F) of DOX was computed as 2.26±0.48 Lkg^-1. The total clearance of DOX (CL_b)was estimated to be 0.29±0.05 Lh^-1kg^-1. The time-point of maximum plasma concentration ofthe drug (T_p) and the maximum plasma concentration (C_max) were calculated as 5.42±0.25h and 1.09±0.26μg/mL. In tissue residue study, DOX was detected in muscle, liver, kidney andskin 7 days after oral administration at a dose of DOX (5mg/kg b.w.). The results showed thatthe drug concentration of tissue was all lower than maximum residue limit (MRL) in 3 daysafter the last administration.The study of pharmacokinetics revealed that a single dose of 5mg/kg b.w. after oraladministration might be sufficient for the long-term maintenance of therapeutic concentrationin the plasma of DOX. Based on the results of the residue study, to ensure tissues samples aresafe for consumption, it is suggested that WDT should not be less than 3 days.