Influence of Simulated Weightlessness on the Intramuscular and Oral Pharmacokinetics of Promethazine in 12 Human Volunteers

Gandia, Peggy; Saivin, Sylvie; Traon, Anne Pavy-Le; Güell, A; Houin, Georges

doi:10.1177/0091270006291032

Cited by 21 publications

(6 citation statements)

References 58 publications

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“…The relative bioavailability of etacizine was increased during HDT BR (Polyakov et al, 2021). Finally, no relevant differences in PK parameters were observed for orally administered ibuprofen after 1‐day of HDT BR (angle not‐specified) (Idkaidek & Arafat, 2011), whereas 30% increased exposure to promethazine was found after 2‐days of 6° HDT BR, especially when the drug was administered per os (Gandia et al, 2006).…”

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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“…In the process, a 30 % increase in bioavailability was found. A possible cause for this is the prolonged contact time with the intestinal wall of the test subjects in this particular lying position [16]. Furthermore, a faster onset of action of ibuprofen with high dissolution and absorption rates was observed [17].…”

Section: Pharmacokinetics and Pharmacodynamics In Real And Simulated Microgravitymentioning

confidence: 93%

Astrotoxicology

Strey¹

2019

Preprint

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After astrochemistry and astrobiology, astrotoxicology is a further subfield of astroscience. Astrotoxicology is an interdisciplinary science that combines physics, biology, chemistry, astronomy, medicine and toxicology. Unlike toxicology on Earth, astrotoxicology in space must take into account the specific features of extreme conditions such as gravity, radiation, temperature or pressure and also consider the distinctions of extreme conditions on other celestial bodies. The field of action of astrotoxicology is, therefore, the influence of lower gravity on the toxicological characteristics of substances in the human body, the special dangers caused by increased radiation in space and on other planets and the special chemical changes caused by the extreme conditions in space on substances and the toxicological consequences associated with them. Despite growing space research, there are so far only a few pharmacokinetic, pharmacodynamic or toxicological investigations under conditions of microgravity and knowledge of toxicology under the extreme conditions in space in particular. Future studies will be the beginning of astrotoxicology, a previously unknown branch of toxicology.

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Influence of Simulated Weightlessness on the Intramuscular and Oral Pharmacokinetics of Promethazine in 12 Human Volunteers

Cited by 21 publications

References 58 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

Astrotoxicology

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