Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne Street, Houston, TX, 77004, USA.
Department of Palliative, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, 77030, TX, USA.
Sci Rep. 2021 Jan 28;11(1):2605. doi: 10.1038/s41598-021-82044-3.
To investigate the effect of simulated weightlessness on the pharmacokinetics of orally administered moxifloxacin and the antacid Maalox or the antidiarrheal Pepto-Bismol using a tail-suspended (TS) rat model of microgravity. Fasted control and TS, jugular-vein-cannulated, male Sprague-Dawley rats received either a single 5 mg/kg intravenous dose or a single 10 mg/kg oral dose of moxifloxacin alone or with a 0.625 mL/kg oral dose of Maalox or a 1.43 mL/kg oral dose of Pepto-Bismol. Plasma concentrations of moxifloxacin were measured by HPLC. Pharmacokinetic data were analyzed using WinNonlin. Simulated weightlessness had no effect on moxifloxacin disposition after intravenous administration but significantly decreased the extent of moxifloxacin oral absorption. The coadministration of moxifloxacin with Maalox to either control or TS rats caused significant reductions in the rate and extent of moxifloxacin absorption. In contrast, the coadministration of moxifloxacin with Pepto-Bismol to TS rats had no significant effect on either the rate or the extent of moxifloxacin absorption. These interactions showed dose staggering when oral administrations of Pepto-Bismol and moxifloxacin were separated by 60 min in control rats but not in TS rats. Dose staggering was more apparent after the coadministration of Maalox and moxifloxacin in TS rats.
为了研究模拟失重对口服莫西沙星的药代动力学的影响，采用尾吊（TS）大鼠模型进行了研究。禁食对照和 TS 、颈静脉插管雄性 Sprague-Dawley 大鼠分别给予单剂量 5mg/kg 静脉注射或单剂量 10mg/kg 口服莫西沙星，或同时给予 0.625ml/kg 口服 Maalox 或 1.43ml/kg 口服 Pepto-Bismol。采用 HPLC 法测定莫西沙星的血浆浓度。采用 WinNonlin 分析药代动力学数据。模拟失重对静脉给药后莫西沙星的处置没有影响，但显著降低了莫西沙星口服吸收的程度。莫西沙星与 Maalox 同时给予对照或 TS 大鼠，均显著降低了莫西沙星的吸收速率和程度。相反，莫西沙星与 Pepto-Bismol 同时给予 TS 大鼠，对莫西沙星的吸收速率或程度均无显著影响。这些相互作用在对照大鼠中，当口服 Pepto-Bismol 和莫西沙星之间间隔 60 分钟时，表现出剂量错开现象，但在 TS 大鼠中则没有。在 TS 大鼠中，莫西沙星与 Maalox 同时给药时，剂量错开现象更为明显。
