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

Polyakov, A.V.; Svistunov, Andreу A; Кондратенко, С. Н.; Kovachevich, I. V.; Repenkova, L. G.; Savelyeva, Marina I.; Кукес, В. Г.

doi:10.1007/s10517-020-04732-w

Cited by 6 publications

(3 citation statements)

References 7 publications

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“…However, as mentioned above, different cohorts of subjects and different specimens were used to assess acetaminophen PK in these two settings thus precluding solid conclusions (Polyakov et al, 2021). In the same study, the authors also considered the PK of different anti‐arrhythmic drugs, namely verapamil, propranolol and etacizine, in part previously published (Polyakov et al, 2020), and the diuretic furosemide. As summarized in Table 3, the exposure to 8° HDT BR for 2 days significantly impacted only on the PK of etacizine, with a significant delay in the absorption, reduced peak concentrations and increased V d .…”

Section: Drug Pk Studies In Space and In Surrogate Models Of Microgra...mentioning

confidence: 99%

Physiological adaptations affecting drug pharmacokinetics in space: what do we really know? A critical review of the literature

Russo

Bandiera

Monici

et al. 2022

British J Pharmacology

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As human spaceflight progresses with extended mission durations, the demand for effective and safe drugs will necessarily increase. To date, the accepted medications used during missions (for space motion sickness, sleep disturbances, allergies, pain, and sinus congestion) are administered under the assumption that they act as safely and efficaciously as on Earth. However, physiological changes have been documented in human subjects in spaceflight involving fluid shifts, muscle and bone loss, immune system dysregulation, and adjustments in the gastrointestinal tract and metabolism. These alterations may change the pharmacokinetics (PK) and pharmacodynamics of commonly used medications. Frustratingly, the information gained from bed rest studies and from in‐flight observations is incomplete and also demonstrates a high variability in drug PK. Therefore, the objectives of this review are to report (i) the impact of the space environmental stressors on human physiology in relation to PK; (ii) the state‐of‐the‐art on experimental data in space and/or in ground‐based models; (iii) the validation of ground‐based models for PK studies; and (iv) the identification of research gaps.

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Section: Drug Pk Studies In Space and In Surrogate Models Of Microgra...mentioning

confidence: 99%

Physiological adaptations affecting drug pharmacokinetics in space: what do we really know? A critical review of the literature

Russo

Bandiera

Monici

et al. 2022

British J Pharmacology

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“…The increased intestinal absorption of AP might be due to the inhibition of intestinal P-gp efflux function under SMG. Additionally, the absorption of P-gp oral drug substrates ibuprofen, Ver, propranolol, and promethazine in humans was promoted under SMG [ 59 , 60 , 61 ]. This finding may also result from the inhibited P-gp efflux function in the intestine under SMG.…”

Section: Discussionmentioning

confidence: 99%

Simulated Microgravity Alters P-Glycoprotein Efflux Function and Expression via the Wnt/β-Catenin Signaling Pathway in Rat Intestine and Brain

Liu

Liang

Deng

et al. 2023

IJMS

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The drug efflux transporter permeability glycoprotein (P-gp) plays an important role in oral drug absorption and distribution. Under microgravity (MG), the changes in P-gp efflux function may alter the efficacy of oral drugs or lead to unexpected effects. Oral drugs are currently used to protect and treat multisystem physiological damage caused by MG; whether P-gp efflux function changes under MG remains unclear. This study aimed to investigate the alteration of P-gp efflux function, expression, and potential signaling pathway in rats and cells under different simulated MG (SMG) duration. The altered P-gp efflux function was verified by the in vivo intestinal perfusion and the brain distribution of P-gp substrate drugs. Results showed that the efflux function of P-gp was inhibited in the 7 and 21 day SMG-treated rat intestine and brain and 72 h SMG-treated human colon adenocarcinoma cells and human cerebral microvascular endothelial cells. P-gp protein and gene expression levels were continually down-regulated in rat intestine and up-regulated in rat brain by SMG. P-gp expression was regulated by the Wnt/β-catenin signaling pathway under SMG, verified by a pathway-specific agonist and inhibitor. The elevated intestinal absorption and brain distribution of acetaminophen levels also confirmed the inhibited P-gp efflux function in rat intestine and brain under SMG. This study revealed that SMG alters the efflux function of P-gp and regulates the Wnt/β-catenin signaling pathway in the intestine and the brain. These findings may be helpful in guiding the use of P-gp substrate drugs during spaceflight.

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“…A somewhat fantastic approach to determining the characteristics and features of "old" drugs, along with determining their impact on modern antiarrhythmic targets, is a new research direction -the study of pharmacokinetics and pharmacodynamics in conditions close to spaceflight. Interestingly, one of the first AADs of the subclass IC to be studied in this sense was ethacizine, which was analysed in the study together with representatives of other classes -verapamil and propranolol (Polyakov et al, 2020).…”

Section: The Place Of Ethacizine In Up-to-date Arrhythmologymentioning

confidence: 99%

Class IC Antiarrhythmic Drugs: Informed Choice

Sydorova

2023

Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences.

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The article presents data on the most commonly used antiarrhythmic drugs of subclass IC: propafenone, flecainide, and a drug manufactured in Latvia — ethacizine. The features and priority areas of each drug use were identified. The author conducted a critical analysis of the results of Cardiac Arrhythmia Suppression Trials (CAST)-I and CAST-II and suggested ways to further study of subclass IC antiarrhythmic drugs in the context of current treatment strategies. The results of CAST-I and CAST-II should be interpreted in view of the heterogeneity of the subclass IC antiarrhythmic drugs and the fact that among the drugs of this subclass that are currently registered and approved for use in Ukraine, only flecainide was studied in CAST-I, and none of these drugs — in CAST-II. Ethacizine has a special position as a promising drug, especially effective in the treatment of vagus-induced heart rhythm disorders, with a small number of contraindications and drug interactions compared with propafenone and flecainide. Despite many years of use in several countries, this drug remains “invisible” to researchers around the world due to a limited number of international studies. The author draws attention to the need to re-evaluate antiarrhythmic drugs with an outdated evidence, in some cases quite limited, and to plan new experimental studies to clarify the possibility of subclass IC drugs to influence new pharmacological targets in arrhythmology, as well as large-scale well-planned studies of the safety and efficacy of subclass IC antiarrhythmic drugs in real present-day clinical practice.

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

Cited by 6 publications

References 7 publications

Physiological adaptations affecting drug pharmacokinetics in space: what do we really know? A critical review of the literature

Physiological adaptations affecting drug pharmacokinetics in space: what do we really know? A critical review of the literature

Simulated Microgravity Alters P-Glycoprotein Efflux Function and Expression via the Wnt/β-Catenin Signaling Pathway in Rat Intestine and Brain

Class IC Antiarrhythmic Drugs: Informed Choice

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