Evaluation of the stability of furosemide in tablet form during six-month storage in spaceflight and peculiarities of its pharmacokinetics and pharmacodynamics under conditions of anti-orthostatic hypokinesia

Abstract

Objectives: The present study investigated the stability of furosemide under space-flight conditions on board the International Space Station, as well as its pharmacokinetics and pharmacodynamics under conditions simulating exposure to some space-flight factors.

Methods: Quantitative analysis of furosemide tablets by HPLC was performed before spaceflight (background), then after six months storage under normal ground conditions (control) and under spaceflight conditions (SF). The pharmacokinetics and pharmacodynamics of furosemide were studied in six healthy volunteers after a single oral dose of 40 mg under normal conditions (background) and under anti-orthostatic hypokinesia (ANOH).

Results: Quantitative content of furosemide in tablets before SF was 40.19 ± 0.28 mg (100.47 ± 0.71%), after 6 months storage: under normal conditions (control) - 39.9 ± 0.39 mg (99.73 ± 0.98%), under SF - 39.24 ± 0.72 mg (98.11 ± 1.80%), which was within the prescribed limits. Studying basic hemodynamic parameters showed that in ANOH conditions 6 h after furosemide administration there was a statistically significant increase of the stroke volume (SV) (+36.5 Δ%), a tendency for increasing of the stroke index (SI) (+36.5 Δ%) and decreasing of the total peripheral resistance (TPR) (-21.9 Δ%) compared to baseline study.

Conclusions: It has been established that various factors of space flight (overloading, excessive vibration, microgravity, etc.) do not negatively influence the stability of furosemide in tablet form during storage for 6 months on board the International Space Station.

Keywords: anti-orthostatic hypokinesia; furosemide; hemodynamics; pharmacodynamics; pharmacokinetics; spaceflight; stability.