The Pharmacokinetics Study Of Roxithromycin Injection In Dogs

Roxithromycin (RXM) is a semisynthetic macrolides antibiotic with a broad and essentially bateriostatic action against many Gram-positive and some Gram-negative bacteria,as well as some anaerobes. Roxithromycin has been widely used clinically to treat a variety of tissues and organs infection,especially as the first picked medicine to therapy pediatric respiratory tract infection. Late years, go with the new found of Pharmacological Action and the new use in non-infection about macrolide antibiotics, enlarge continually clinical uses of roxithromycin. In order to adapt to the demand of clinical uses,and offer multi-choice to medical staff and patients,inclusion compound of roxithromycin can be prepared by reaction with hydroxypropyl-β-cyclodextrin, roxithromycin injection prepared from the inclusion compound may fill up the vacancy that roxithromycin was not injection preparation.Luoyonghuang and tangyan had processed the thermal stability, in vitro antibacterial activities, acute toxicity test and special toxicity test of roxithromycin injection.as to a new drug or dosage form,the pharmacokinetics study is a work that must be done in the preclinical test.Therefore, to study the transformation of blood drug level in different time and the pharmacokinetics parameters after a single intramuscular administration of roxithromycin injection,and investigate the pharmacokinetics characteristic and relative bioavailability of roxithromycin injection by comparing with the roxithromycin dispersible tablets,roxithromycin clathrate capsule clathrated with HP-β-CD and roxithromycin material powder capsule in dogs. Single intramuscular administration of 300mg of roxithromycin injection and a single oral administration of 300mg of roxithromycin dispersible tablets,roxithromycin clathrate capsule clathrated with HP-β-CD and roxithromycin material powder capsule were given to 6 dogs in a randomized crossover design. The drug concentration in plasma were deternined by reversed-phase HPLC and UV detctor. Pharmacokinetics software was used in calculation of compartment model and pharmacokinetics parameters,the relative bioavailahility were measured. Results , the pharmacokinetics parameters of roxithromycin injection,roxithromycin dispersible tablets,roxithromycin clathrate capsule clathrated with HP-β-CD and roxithromycin material powder capsule were respectively as follows: C_max12.228μg/mL9.252μg/mL,5.204μg/mL and 2.307μg/mL; T_max 1.489h,3.189h,4.398h and 2.44272h; AUC_0-481.467L/Kg,2.242 L/Kg,3.625L/Kg and 5.44L/Kg; t_1/29.534h,13.830h,32.8h and 3.638h; CL_B 0.106 L/kg.h,0.112 L/kg.h,0.464 L/kg.h和1.036 L/kg.h; the relative bioavailability were respectively 105.31%, 79.11% and 10.83%; roxithromycin injection was one-compartment model, roxithromycin dispersible tablets was two-compartment model , roxithromycin clathrate capsule clathrated with HP-β-CD was two-compartment model, and the roxithromycin material powder capsule was one-compartment model.The pharmacokinetics parameters of roxithromycin injection in dogs, compared with roxithromycin dispersible tablets,roxithromycin clathrate capsule clathrated with HP-β-CD and roxithromycin material powder capsule,the pharmacokinetics characteristic of roxithromycin injection was better,and the relative bioavailability was better.