Oral absorption and drug interaction kinetics of moxifloxacin in an animal model of weightlessness

Dong Liang,Jing Ma,Bo Wei

doi:10.1038/s41598-021-82044-3

Dong Liang, Jing Ma + Show 1 more

Open Access

https://doi.org/10.1038/s41598-021-82044-3

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Abstract

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.

Highlights

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
Pharmacokinetic interactions between moxifloxacin and concomitantly administered bismuth subsalicylate under ground control and simulated weightlessness are shown in Fig. 2 and Table 2
In control rats, compared with the administration of moxifloxacin alone, concomitant administration of moxifloxacin 5 min after Pepto-Bismol administration statistically significantly reduced the C max by 49.5% and statistically significantly increased the T1⁄2 by 121%. This T1⁄2 was appreciably longer than that observed after IV administration of moxifloxacin alone to control rats (T1⁄2 = 1.79 h), indicating that bismuth subsalicylate decreases the rate of absorption of moxifloxacin to such an extent that flip-flop kinetics become evident

Summary

Introduction

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. The coadministration of moxifloxacin with Maalox to either control or TS rats caused significant reductions in the rate and extent of moxifloxacin absorption. 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. Metal ions in Maalox (Mg2+ and Al3+) and Pepto-Bismol (Bi3+) could form various types of complexes with moxifloxacin and impact its absorption in the GI tract

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