Effects of high altitude exposure on the pharmacokinetics of furosemide in healthy volunteers

Arancibia, A; Gai, Marı́a Nella; Paulos, Claudio; Chávez, J; Pinilla, Elizabeth; Angel, N; Ritschel, W. A.

doi:10.5414/cpp42314

Cited by 18 publications

(12 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At the same time, it has crosscutting relevance to basic medicine, medical psychology and social sciences: from sports medicine and the aerospace industry to urban and rural communities living at high altitude (Shah et al, ). After acute or chronic exposure to high altitude, the pharmacokinetics of conventional drugs such as carbonic anhydrase inhibitors (acetazolamide), antipyretic analgesics (acetylsalicylic acid), corticosteroids (prednisolone), diuretics (furosemide), antibacterial (sulfamethoxazole) and antibiotics (gentamicin) etc., have certified variations (Arancibia et al, , ; Li, Liu, Li, Yuan, & Zhu, ; Vij, Kishore, & Dey, ), in accordance with our previous study of antiarrhythmic drugs (propranolol and metoprolol) (Zhang et al, ). Hence, it is essential to emphasize the importance of the safe treatment of maladies at high altitude.…”

Section: Introductionsupporting

confidence: 89%

Evaluation of renal excretion and pharmacokinetics of furosemide in rats after acute exposure to high altitude at 4300 m

Luo

Yang

et al. 2018

Biopharm & Drug Disp

View full text Add to dashboard Cite

With studies indicative of altered renal excretion under high altitude-induced hypobaric hypoxia, the consideration of better therapeutic approaches has long been the aim of research on the management of high altitude related illness. The pharmacokinetics of drugs such as furosemide might be altered under hypoxic conditions, making it essential to establish different dose-regimens to maintain therapeutic efficacy or to avoid toxic side effects at high altitude. Simultaneously, drug-drug interactions (DDIs) mediated by OAT1 occur at high altitude, severely affecting furosemide pharmacokinetics. This study investigated the influence of acute exposure to high altitude at 4300 m on the renal excretion of furosemide in rats. Significant changes in physiological parameters and kidney histopathology were found after acute high altitude exposure. Compared with low altitude, the pharmacokinetics of furosemide and the expression level of OAT1 in kidney were significantly changed after rapid ascent to high altitude. Additionally, the down-regulated OAT1 expression further sustained the potential mechanism for the decreased renal excretion of furosemide, resulting in extended residence of the drug in the human body. The elevation of AUC, C , MRT, t of furosemide, and decreased CL at high altitude further reinforced the current findings. Moreover, the absorption of furosemide was markedly increased and renal excretion significantly declined after co-administration of captopril, resulting in local drug interaction at high altitude. In conclusion, acute exposure to high altitude may significantly affect the renal excretion of furosemide and the pharmacokinetic parameters of furosemide were altered after co-administration of captopril, which may then impact the conventional therapeutic dosage.

show abstract

Section: Introductionsupporting

confidence: 89%

Evaluation of renal excretion and pharmacokinetics of furosemide in rats after acute exposure to high altitude at 4300 m

Luo

Yang

et al. 2018

Biopharm & Drug Disp

View full text Add to dashboard Cite

show abstract

“…Some studies have performed on the effects of exposure to high altitude on the pharmacokinetics of drugs. LI Xiang-yang et al (2010) found significant changes in the pharmacokinetics of sulfamethoxazole under hypoxia, the Ke and CL were lower in the acute exposure and chronic exposure groups, compared with the plain group, and the t 1/2 , MRT, t max and AUC were higher in the acute exposure and chronic exposure groups, compared with the plain group; similar results were found in theophylline, prednisone, acetazolamide and demerol at high altitude (Arancibia et al, 2004(Arancibia et al, , 2005Letarte & du Souich, 1984;Powell et al, 1978;Ritschel et al, 1996;Wolfgang et al, 1998). Some previous studies suggest CYP enzymes activity is the major factor, as hypoxia down-regulates CYP1A1, CYP1A2, CYP2B6, CYP2C9 and CYP2C19, decrease preceded by a reduction in activity.…”

Section: Introductionsupporting

confidence: 83%

MDR1 will play a key role in pharmacokinetic changes under hypoxia at high altitude and its potential regulatory networks

Wang

et al. 2015

Drug Metabolism Reviews

View full text Add to dashboard Cite

Some newest studies indicated that drug transports may play the key role in pharmacokinetics changes under hypoxia at high altitude; MDR1 is now known to affect the disposition of many administered drugs and make a major contribution to absorption, distribution, metabolism, excretion. Different expression of MDR1 is frequently found in different normal tissues and tumor cells; it is important to better understand how MDR1 is regulated under hypoxia, which seems to be a complex and highly controlled process. Several signaling pathways and transcription factors have been described as being involved in the regulation of MDR1 expression, such as MAPK/ERK, nuclear factor-kappaB, hypoxia-inducible factor-1a, pregnane × receptor, constitutive androstane receptor and microRNA. Recently, researches have been increasingly appreciating long non-coding RNAs (lncRNAs) as an integral component of gene regulatory networks. lncRNAs play crucial roles in various biological processes ranging from epigenetic gene regulation, transcriptional control, post-transcriptional regulation, pre-mRNA processing and nuclear organization. A last recent research showed that H19 gene non-coding RNA is believed to induce P-glycoprotein expression under hypoxia.

show abstract

“…Analgesics and antihypertensives are mostly studied under various hyperthermic and hypothermic conditions lasting from hours to a few days. High altitude (hypoxia) alters the pharmacokinetics of certain analgesics, 10 , 11 anti‐hypertensives, 12 – 14 asthma, 14 , 15 mountain sickness, 16 , 17 and alertness medications 18 . The physiological effects of high altitude could last for months.…”

Section: Resultsmentioning

confidence: 99%

“…The physiological effects of high altitude could last for months. However, there are several studies that demonstrated no effects, 13 – 15 , 19 while others showed drug‐dependent effects on elimination, 11 , 17 and plasma concentration 12 , 18 . Although hyperbaric stress could enhance the clearance of salicylic acid in animals, 20 evidence from human studies is not available.…”

Section: Resultsmentioning

confidence: 99%

A Review of Psychophysiological Stressors on Pharmacokinetics

Peng

Cheung

2011

The Journal of Clinical Pharmacology

View full text Add to dashboard Cite

We conducted a comprehensive literature review on the effects of psychophysiological stressors on the pharmacokinetics of drugs commonly used by the Canadian Forces. These stressors may change the physiological status of an individual and subsequently may alter the drug's pharmacokinetics. The effects of isolated physical activities on pharmacokinetics have been well documented. However, the findings are inconsistent due to variations in the intensity and duration of the activity, and the routes and timing of drug administration. The effects of other environmental stressors, such as temperature extremes, hypobaric, hyperbaric, hyperoxic conditions, and the effects of multiple stressors are less well known. There are limited studies describing the effects of psychological stressors on drug pharmacokinetics. Further studies are necessary to understand the clinical implications of pharmacokinetic changes. We also discussed the advantage of using a physiologically based pharmacokinetic model to predict the effects of a single or multiple stressors.

show abstract

Effects of high altitude exposure on the pharmacokinetics of furosemide in healthy volunteers

Cited by 18 publications

References 0 publications

Evaluation of renal excretion and pharmacokinetics of furosemide in rats after acute exposure to high altitude at 4300 m

Evaluation of renal excretion and pharmacokinetics of furosemide in rats after acute exposure to high altitude at 4300 m

MDR1 will play a key role in pharmacokinetic changes under hypoxia at high altitude and its potential regulatory networks

A Review of Psychophysiological Stressors on Pharmacokinetics

Contact Info

Product

Resources

About