Effects of High Altitude Exposure on Physiology and Pharmacokinetics

Lu, Hui; Wang, Rong; Zeng, Jia; Xiong, Juan; Xie, Haiyang

doi:10.2174/1389200216666151015113948

Cited by 16 publications

(16 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, further studies are required to confirm the role of altitude in the duration to cure of PTB patients. Second, according to Hui et al [63], the pharmacokinetics of drugs changes at high altitudes, so that in order to maintain the effect of the drug for a certain period of time, it is necessary to modify the dose of the treatment regimen in the highlands. In addition, it was revealed that pretreatment weight was inversely associated with duration to cure.…”

Section: Discussionmentioning

confidence: 99%

Bayesian Spatial Survival Analysis of Duration to Cure among New Smear-Positive Pulmonary Tuberculosis (PTB) Patients in Iran, during 2011–2018

Nazar

Baghishani

Doosti

et al. 2020

IJERPH

View full text Add to dashboard Cite

Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), and pulmonary TB is the most prevalent form of the disease worldwide. One of the most concrete actions to ensure an effective TB control program is monitoring TB treatment outcomes, particularly duration to cure; but, there is no strong evidence in this respect. Thus, the primary aim of this study was to examine the possible spatial variations of duration to cure and its associated factors in Iran using the Bayesian spatial survival model. All new smear-positive PTB patients have diagnosed from March 2011 to March 2018 were included in the study. Out of 34,744 patients, 27,752 (79.90%) patients cured and 6992 (20.10%) cases were censored. For inferential purposes, the Markov chain Monte Carlo algorithms are applied in a Bayesian framework. According to the Bayesian estimates of the regression parameters in the proposed model, a Bayesian spatial log-logistic model, the variables gender (male vs. female, TR = 1.09), altitude (>750 m vs. ≤750 m, TR = 1.05), bacilli density in initial smear (3+ and 2+ vs. 1–9 Basil & 1+, TR = 1.09 and TR = 1.02, respectively), delayed diagnosis (>3 months vs. <1 month, TR = 1.02), nationality (Iranian vs. other, TR = 1.02), and location (urban vs. rural, TR = 1.02) had a significant influence on prolonging the duration to cure. Indeed, pretreatment weight (TR = 0.99) was substantially associated with shorter duration to cure. In summary, the spatial log-logistic model with convolution prior represented a better performance to analyze the duration to cure of PTB patients. Also, our results provide valuable information on critical determinants of duration to cure. Prolonged duration to cure was observed in provinces with low TB incidence and high average altitude as well. Accordingly, it is essential to pay a special attention to such provinces and monitor them carefully to reduce the duration to cure while maintaining a focus on high-risk provinces in terms of TB prevalence.

show abstract

Section: Discussionmentioning

confidence: 99%

Bayesian Spatial Survival Analysis of Duration to Cure among New Smear-Positive Pulmonary Tuberculosis (PTB) Patients in Iran, during 2011–2018

Nazar

Baghishani

Doosti

et al. 2020

IJERPH

View full text Add to dashboard Cite

show abstract

“…Hypoxia can cause dysfunction, damage and death to cells, tissues and organisms, and is associated with many pathophysiological processes and diseases such as stroke, asthma, emphysema, angina pectoris, myocardial infarction and tumors [1,2]. Hypoxia induced at high altitude also causes a subnormal oxygen concentration in cells which affects the drug metabolic and pharmacokinetic capacity [9].…”

Section: Effect Of Alt and Sea On The Pharmacokinetics Of Diclofenac Sodium And Cefadroxilmentioning

confidence: 99%

“…A series of physiological systems reacting to a high-altitude stressor and the effects of these physiological alterations on pharmacokinetics have been investigated for decades . The effects of high altitude on human physiological alterations (including those in the gastrointestinal system, cardiovascular system, pulmonary system, hematocrit, drug metabolism enzyme system, and renal excretory system), as well as subsequent changes of pharmacokinetics (such as absorption, distribution, metabolism, and excretion of drugs)(ADME) [1][2][3][4][5][6][7][8][9]. High altitudes can lead to a broad range of physiological changes, leading to the changes in the ADME process of drugs [10][11][12][13][14][15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

“…High altitudes can lead to a broad range of physiological changes, leading to the changes in the ADME process of drugs [10][11][12][13][14][15][16][17][18][19][20]. According to previous pharmacokinetics studies in human, the pharmacokinetics changes due to high altitude exposure may require dosage regimen modifications to maintain drug efficacy and safety, which should draw our attention to drug administration dosage for those planning ascent to high altitudes [1][2][3][21][22][23][24][25][26][27][28][29][30][31][32][33]. Previous studies have demonstrated hypoxia at high altitude can adversely affect both drug metabolism and toxicity [21][22][23][24][25][26][27][28][29][30][31][32][33].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Altitude (2500 M) on The Pharmacokinetics of Diclofenac Sodium and Cefadroxil After Oral Administration To Human Volunteers

Mohammed¹,

Hussein²

2018

AJPHR

View full text Add to dashboard Cite

This paper reports, for the first time, the data on the pharmacokinetic characteristics of diclofenac sodium and cefadroxil at Albaha, 2500 M altitude (ALT) , KSA. Therefore, the objective of this study was to compare the plasma concentrations and pharmacokinetic parameters of diclofenac sodium (Voltaren  50 tablets, Ciba Geigy, USA) and cefadroxil (Ultrcef  500 capsules, Bristol L. Germany) at altitude of 2500 M (ALT) and at sea level (SEA) after oral administration to 12 healthy volunteers. A two-way cross over study design was used to compare pharmacokinetic parameters at ALT and SEA. Following drug administration, blood withdrawn into heparinized test tubes over a period of 12 hours. Drug concentrations were determined in the withdrawn samples by fully validated and optimized HPLC methods for the two drugs. The pharmacokinetic parameters including C max , t max , t 0.5e , t 0.5a , K e , K a , V d , Cl T , AUC 0-12h , and AUC 0-∞ were determined by a computer programs. Statistical analysis of the obtained plasma drug concentrations and pharmacokinetic parameters were performed using ANOVA computerized system. Results obtained showed significant differences in the plasma concentrations and all pharmacokinetic parameters of the two drugs at ALT as compared to SEA. There was a significant increase in C max and AUC 0-12h , of both drugs at ALT as compared to SEA. The values of Vd and Cl T were significantly lower at ALT than SEA. ALT could markedly inhibit the metabolism and renal excretion of both drugs as indicated by significant increase in the elimination half-lives (t 0.5e ) and decrease in the elimination rate constant (K e ) at ALT as compared to SEA. The obtained results clearly indicate that the plasma concentrations and all the pharmacokinetic parameters of both diclofenac sodium and cefadroxil are significantly modified by ALT. Therefore, dosage regiemens adjustment is important when diclofenac sodium and cefadroxil are prescribed for administration at ALT to maintain drug efficacy and safety and to avoid drug , s toxicity.

show abstract

“…People are also scaling to extreme altitudes like Mount Everest 8848 m and other peaks as part of adventure sports [4]. During exposure to a high altitude environment, the human body undergoes many physiological, biochemical, and haematological changes which are required for coping with the environmental stress at high altitude [5]. The physiological and biochemical adjustments include hyperventilation, in ammation, an increase in breathing capacity, and hemoglobin concentration that help to restore oxygen delivery to tissues despite low partial pressure [2,6,7].…”

Section: Introductionmentioning

confidence: 99%

Network Biology led identification of critical miRNA modules for High Altitude hypoxia and their potential as dietary supplements

Gupta¹,

Sugadev²,

Sharma³

et al. 2021

Preprint

View full text Add to dashboard Cite

Early ascent to high altitude can cause severe damage to body functions and may lead to many fatal high-altitude disorders. To cope up with such conditions, the human body undergoes physiological and biochemical changes in order to adapt to extreme environmental conditions at high altitudes. Several microRNAs (miRNAs), Transcription Factors (TFs), and genes have been studied separately for their role in early adaptive molecular responses. We hypothesize that network analysis of miRNA-TF-gene co-regulatory networks of circulatory miRNAs (CmiRNAs) which are differentially expressed at high altitudes could reveal a complex regulatory functional module that might be controlling molecular adaptive responses at high altitude. A comprehensive and non-redundant list of differentially expressed human CmiRNAs during high altitude ascent was collated and 470 Feed-Forward Loops (FFLs) tripartite motifs were identified in the miRNA-TF-gene co-regulatory networks. Network analysis and K-means clustering identified 11 biologically overrepresented FFLs regulated by 8 miRNAs hsa-miR-335-5p, hsa-miR-26a-1-3p, hsa-miR-210-3p, hsa-miR-193b-3p, hsa-miR-17-5p, hsa-miR-16-5p, hsa-miR-5582-5p and hsa-miR-130a-3p. Pathway enrichment identified metabolism and inflammation as important hallmark responses responsible for high altitude adaptation. These miRNAs were evaluated for their supplementation from dietary sources. Phylogenetic analysis with 4 other mammalian and non-mammalian species showed that Bos taurus (cattle) milk could be a possible source of these dietary miRNAs. Exogenous miRNAs bta-mir-16-1, bta-mir-130a, bta-miR-335, and bta-miR-210 have >95% of sequence similarity and could become potential dietary miRNAs candidates. The sequence, structural properties, and high AGO2 binding efficiency of all these exogenous miRNAs show good serum stability and cellular uptake possibility in the mammalian host. Bta-miR-210 with highest Minimal Folding free Energy Index (MFEI) and highest Atomic Contact Energy (ACE) with AGO2 has the best potential to be a dietary supplement.

show abstract

Effects of High Altitude Exposure on Physiology and Pharmacokinetics

Cited by 16 publications

References 0 publications

Bayesian Spatial Survival Analysis of Duration to Cure among New Smear-Positive Pulmonary Tuberculosis (PTB) Patients in Iran, during 2011–2018

Bayesian Spatial Survival Analysis of Duration to Cure among New Smear-Positive Pulmonary Tuberculosis (PTB) Patients in Iran, during 2011–2018

Effect of Altitude (2500 M) on The Pharmacokinetics of Diclofenac Sodium and Cefadroxil After Oral Administration To Human Volunteers

Network Biology led identification of critical miRNA modules for High Altitude hypoxia and their potential as dietary supplements

Contact Info

Product

Resources

About