Drug Release Characteristics and Tissue Distribution of Rifapentine Polylactic Acid Sustained-Release Microspheres in Rabbits after Paravertebral Implantation

نویسندگان

1 Bone Tumor Surgery, First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China

2 Bone Tumor Surgery, First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China

3 Orthopedics Department, Fifth Affiliated Hospital of Xinjiang Medical University, Xinjiang, China

4 Bone Tumor Surgery, First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China

5 Bone Tumor Surgery, First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China

doi
چکیده

ground: Rates of drug-resistant tuberculosis (TB) and TB associated with human immunodeficiency virus (HIV) infection haveincreased dramatically, intensifying challenges in TB control. New formulations of TB treatment drugs that control drug releaseand increase local drug concentrations will have a significant impact on mitigating the toxic side effects and increasing the clinicalefficacy of anti-TB drugs.Objectives: The aim was to observe the sustained release characteristics of rifapentine polylactic acid sustained-release microspheresin vivo and the accumulation of rifapentine in other tissues following paravertebral implantation.Methods: This study is a basic animal experimental study that began on July 17, 2014 in the Fifth Affiliated hospital of Xinjiang MedicalUniversity. One hundred and eight New Zealand white rabbits (weighing 2.8 - 3.0 kg, male and female, China) were randomlydivided into three groups of 36 rabbits each. Blood and tissue samples from the liver, lungs, kidneys, vertebrae, and paravertebralmuscle were collected at different time points post-surgery. High performance liquid chromatography (HPLC) analysis with a biologicalinternal standard was used to determine the drug concentrations in samples.Results: In group A, no significant differences in rifapentine concentrations in the liver were detected between any two time points(P > 0.05). However, the differences in rifapentine concentrations between day 10 and day 21 were statistically significant (P < 0.05);for days 21, 35, 46, and 60, the differences in rifapentine concentrations between two sequential time points were not statisticallysignificant (P> 0.05). IngroupB, the differences in rifapentine concentration between days 3and10 in vertebralboneandin paravertebralmuscles were statistically significant (P < 0.05). Rifapentine was detected in the vertebral bone tissue in the group C animals.The rifapentine concentrations between two sequential time points were statistically significant (P < 0.05). Rifapentine could notbe detected in the paravertebral muscles 46 days after the operation. The differences in rifapentine concentrations between twosequential time points among days 3, 10, 21, and 35 were statistically significant (P < 0.05).Conclusions: After paravertebral implantation of rifapentine polylactic acid sustained-release microspheres, the concentration ofrifapentine in local vertebral bone tissues was maintained above the TB minimum inhibitory concentration for up to 60 days withno apparent accumulation of the drug in other tissues.