Study of the pharmacokinetics of various drugs under conditions of antiorthostatic hypokinesia and the pharmacokinetics of acetaminophen under long-term spaceflight conditions.

Objectives: To study the pharmacokinetics and relative bioavailability of drugs of different chemical structure and pharmacological action under conditions simulating the effects of some factors of spaceflight, as well as the peculiarities of the pharmacokinetics of acetaminophen under long-term spaceflight conditions.

Methods: The pharmacokinetics of verapamil (n=8), propranolol (n=8), etacizine (n=9), furosemide (n=6), and acetaminophen (n=7) in healthy volunteers after a single oral administration under normal conditions (background) and under antiorthostatic hypokinesia (ANOH), the pharmacokinetics of acetaminophen in spaceflight members under normal ground conditions (background) (n=8) and under prolonged spaceflight conditions (SF) (n=5) were studied.

Results: The stay of volunteers under antiorthostatic hypokinesia had different effects on the pharmacokinetics and bioavailability of drugs: Compared to background, there was a decreasing trend in V for verapamil (-54 Δ%), furosemide (-20 Δ%), propranolol (-8 Δ%), and acetaminophen (-9 Δ%), but a statistically significant increase in V was found for etacizine (+39 Δ%); there was an increasing trend in Cl for propranolol (+13 Δ%) and acetaminophen (+16 Δ%), and a decreasing trend in Cl for etacizine, verapamil, and furosemide (-22, -23 and -9 Δ% respectively) in ANOH.

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.

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).

Study of the pharmacokinetics of various drugs under conditions of antiorthostatic hypokinesia and the pharmacokinetics of acetaminophen under long-term spaceflight conditions.

Objectives: To study the pharmacokinetics and relative bioavailability of drugs of different chemical structure and pharmacological action under conditions simulating the effects of some factors of spaceflight, as well as the peculiarities of the pharmacokinetics of acetaminophen under long-term spaceflight conditions.

Methods: The pharmacokinetics of verapamil (n=8), propranolol (n=8), etacizine (n=9), furosemide (n=6), and acetaminophen (n=7) in healthy volunteers after a single oral administration under normal conditions (background) and under antiorthostatic hypokinesia (ANOH), the pharmacokinetics of acetaminophen in spaceflight members under normal ground conditions (background) (n=8) and under prolonged spaceflight conditions (SF) (n=5) were studied.

Results: The stay of volunteers under antiorthostatic hypokinesia had different effects on the pharmacokinetics and bioavailability of drugs: Compared to background, there was a decreasing trend in V for verapamil (-54 Δ%), furosemide (-20 Δ%), propranolol (-8 Δ%), and acetaminophen (-9 Δ%), but a statistically significant increase in V was found for etacizine (+39 Δ%); there was an increasing trend in Cl for propranolol (+13 Δ%) and acetaminophen (+16 Δ%), and a decreasing trend in Cl for etacizine, verapamil, and furosemide (-22, -23 and -9 Δ% respectively) in ANOH.

Peculiarities of Pharmacokinetics and Bioavailability of Some Cardiovascular Drugs under Conditions of Antiorthostatic Hypokinesia.

We studied pharmacokinetics and bioavailability of verapamil, propranolol, and ethacizine in healthy volunteers after single oral administration under normal conditions and on the second day of simulated antiorthostatic hypokinesia modeling some effects of microgravity. Under conditions of antiorthostatic hypokinesia, a tendency to a decrease in half-elimination period, mean retention time, and volume of distribution and an increase in the rate of absorption, ratio of maximum concentrations, and relative rate of absorption of verapamil and propranolol were revealed. For ethacizine, a statistically significant increase in the time of attaining maximum concentration and volume of distribution and a decrease in the maximum concentration, rate of absorption, ratio of maximum concentrations, and relative rate of absorption under conditions of antiorthostatic hypokinesia were found.

PROPRANOLOL PHARMACOKINETICS AND HEMODYNAMIC INDICES IN ANTIORTHOSTATIC HYPOKINESIA.

Purpose of the work was to study pharmacokinetics of beta adrenoblocker propranolol, and hemodynamic indices in volunteers for simulation of some effects of microgravity The study involved 8 essentially healthy subjects and the head-down tilt (-80) bedrest model reproducing the effects of microgravity (BD). This was designed as three series of investigations, i.e.

[TESTING STABILITY OF TABLETED ACETAMINOPHEN AND FUROSEMIDE AFTER 6-MONTH STORAGE IN SPACE FLIGHT].

It was shown that multiple spaceflight factors (i.e., acceleration, overvibration, microgravity etc.

[Medical care for Russian cosmonauts' health on the ISS].

Established with the personal participation of O.G. Gazenko, the Russian system of medical care for cosmonauts' health has been largely preserved till this day.

[Medical provisions for non-career cosmonauts on short-duration flights to the International Space Station].

The paper presents the factual data about 6 participants in short-duration space flights of three age groups (according to the WHO classification). The scope of medical care for three young SFPs whose health status was qualified as good replicated the program adopted in Russia for crewmembers trained for short-duration orbital flights. To safeguard three SFPs of middle and elderly age among whom two had deviations in body functions, the standard medical care program was reinforced by prescription of corrective pharmaceuticals to be taken during space flight, supply of personal kits with preventive medicine, inclusion of additional examinations into the standard medical monitoring and modification of the in-flight countermeasure program, if necessary.

[The cardiovascular function and etacizin pharmacokinetics during antiorthostatic hypokinesia].

A comprehensive comparative study of etacizin (an antiarrythmic drug) pharmacokinetics and cardiovascular effects was performed with participation of nine subjects in usual circumstances and during 7-d head-down tilt (HDT, -8 degrees). Drug concentration in blood plasma was determined by HPLC with the spectrophotometric method; the cardiovascular function was evaluated based on ECG, tachycardiography, and rheography. HDT was shown to markedly reduce maximal concentration of the drug.

In-flight medical incidents in the NASA-Mir program.

This paper summarizes medical experience during the six NASA-Mir flights from March 14, 1995, to June 4, 1998. There were 7 U.S.

[Several clinical aspects of a piloted Martian flight].

The authors consider factors and risk sources in long and superlong (interplanetary) missions, conceivable effects of extended exposures in microgravity, and probability of diseases in the crew. They also lay down the basic principles of medical care, including surgery, to be applied in the interplanetary mission, and propose a nomenclature of key means and equipment for the therapeutic and emergency medical care, and a configuration of a medical compartment.

Medical care system for NASA-Mir spaceflights.

A fundamental goal of space medicine is to maintain the health and fitness of spacecrews. Meeting this goal requires reliable, effective, up-to-date medical support systems for use in microgravity. This article describes some of the factors considered in the design and assembly of Russian and U.

[The pharmacodynamic and pharmacokinetic characteristics of furosemide and furesis].

The object of the work was comparative study of the special features of the pharmacodynamic and pharmacokinetic properties of the diuretics furosemide and furesis in an ambulant regimen with the subject lying in an antiorthostatic position. Six practically healthy males were examined. They were given per os either 40 mg furosemide or one tablet of furesis (49 mg furosemide and 50 mg triamterine).

[The pharmacodynamics and pharmacokinetics of furosemide during ordinary life activities and during head-down tilt hypokinesia in a healthy subject].

The object of the work was comparative study of the characteristics of pharmacodynamics and pharmacokinetics of the diuretic furosemide during ordinary vital activity of man and under conditions of antiorthostatic hypokinesia. Six practically healthy males were examined. They took part successively in two experimental series: series 1--during an ordinary motor regimen under ambulatory conditions; series 2--under conditions of antiorthostatic hypotension (ANOH, 12 degrees).

Blunt trauma and operative care in microgravity: a review of microgravity physiology and surgical investigations with implications for critical care and operative treatment in space.

Background: The assembly of the International Space Station in a low earth orbit will soon become a reality. The National Aeronautics and Space Administration envisions inhabited lunar bases and staffed missions to Mars in the future. Increasing numbers of astronauts, construction of high-mass structures, increased extra-vehicular activity, and prolonged if not prohibitive medical evacuation times to earth underscore the need to address requirements for trauma care in nonterrestrial environments.

[Changes in regional pulmonary hemodynamics and levels of vasoactive substances in man in a state of antiorthostatic hypokinesia].

A comparative evaluation of rheographic changes in regional pulmonary hemodynamics and renin-angiotensin and kinin-kallikrein activities was carried out on 9 volunteers exposed to antiorthostatic hypokinesia (-8 degrees) for 14 days. It was found that pulmonary circulation shifted in the apical direction due to increase in arterial tonicity and phasic variations of venous lumen. During the study blood renin increased significantly (P less than 0.

[Clinico-physiological aspects of the tissue oxygen supply of the human body during head-down tilt hypokinesia].

In three antiorthostatic hypokinesia studies of varying duration gas exchange, central and regional hemodynamics were investigated. The hypokinetic effect on oxygen changes in the human body was evaluated by comparing the above results with biochemical data. It is concluded that bed rested subjects developed hypoxic changes of mixed circulatory-respiratory type.

[Status of metabolism and peripheral circulation in man during antiorthostatic hypokinesia].

Metabolism and peripheral circulation were investigated in head-down tilt tests of varying duration. The greatest changes were seen on test day 30 when the subjects showed venous hyperoxia, lower oxygen arterio-venous difference and a significant (p less than 0.05) decrease of oxygen tension in arterial blood and oxygen utilization in tissues (p less than 0.

[Changes in regional hemodynamics and gas exchange in healthy males after moderate blood loss and blood reinfusion in response to antiorthostatic hypokinesia].

Nine healthy male test subjects were exposed for 7 days to head-down tilting. Within 2 hours after exposure 500 ml of blood were withdrawn. This reduced pulse blood filling of all lung compartments, particularly upper (P less than 0.

[Effect of head-down-tilt hypokinesia on pulmonary blood flow and gas exchange].

The purpose of the study was to investigate gas exchange and lung perfusion during 14-day head-down tilt and immediately thereafter. During head-down tilting pulmonary circulation increased, as suggested by zonal rheography of the lungs and by ECG (increase in the PII-III amplitude and width by 1-2 mm and 0.01-0.