title: Comparative pharmacokinetics of continuous and conventional intrathecal amphotericin B in rabbits.
abstract: We previously reported a new effective therapy, continuous intrathecal amphotericin B (AMB), for the treatment of cryptococcal meningitis, which had fewer side effects and complications than conventional intrathecal AMB. In this study, the pharmacokinetics of continuous intrathecal administration and conventional intrathecal AMB were compared in rabbits, providing a pharmacokinetic basis for the use of continuous intrathecal AMB therapy. The AMB concentration in the cerebrospinal fluid (CSF), sampled via an inserted cisterna magna catheter, was determined by a liquid chromatography-tandem mass spectrometry assay. The results revealed significant pharmacokinetic differences between the two groups. In the continuous intrathecal group (0.15 mg/kg/24 h), the concentration of AMB peaked 7.01 μg/ml at 4 h and then decreased to a stable level of 1.0 to 1.34 μg/ml, with no neurological impairments, while in the conventional intrathecal group (0.015 mg/kg), the drug concentration reached a peak of 3.41 μg/ml at 1 h and then decreased progressively, with fever and neurological impairments, including convulsion and paralysis. The pharmacokinetic results indicated that the continuous intrathecal AMB is a more effective and safe therapy than the conventional intrathecal AMB, with comparatively rational pharmacokinetics and fewer neurological impairments.
authors: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China.
authors: Min
authors: M
authors: Fang
authors: Tian Ming
authors: TM
authors: Lü
authors: An De
authors: AD
authors: Ma
authors: Li
authors: L
authors: Wang
authors: Guo Liang
authors: GL
authors: Li
authors: Ai Zhu
authors: AZ
authors: Qiu
authors: Zhi Yong
authors: ZY
authors: Pan
authors: Yuan Yuan
authors: YY
authors: Wang
authors: Xiao Jia
authors: XJ
authors: Liu
mesh_terms: D000666:Amphotericin B / Q000493:pharmacokinetics*; D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics*; D011817:Rabbits; D013346:Subarachnoid Space / Q000648:ultrastructure
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B