scholarly journals Changes in the Pharmacokinetics and Pharmacodynamics of Sildenafil in Cigarette and Cannabis Smokers

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 876
Author(s):  
Mohammed Murtadha ◽  
Mohamed Ahmed Raslan ◽  
Sarah Farid Fahmy ◽  
Nagwa Ali Sabri
Keyword(s):  
Primary Outcome ◽  
Human Subjects ◽  
Inhibitory Effect ◽  
Healthy Human ◽  
Time Curve ◽  
Cigarette Smokers ◽  
Enzyme Substrate ◽  
Elimination Half ◽  
Cyp3a4 Enzyme

Sildenafil citrate, a widely-used oral therapy for erectile dysfunction, is a cytochrome P3A4 (CYP3A4) enzyme substrate. Studies have reported that this substrate has an inhibitory effect on CYP3A4 enzymes in long-term cigarette and cannabis smokers, which predominantly mediate the hepatic elimination of sildenafil. Cigarette and/or cannabis smoking could therefore alter the exposure of sildenafil. The aim of this study was to examine the effect of smoking cigarettes and/or cannabis on the pharmacokinetics, pharmacodynamics, safety and tolerability of sildenafil. Thirty-six healthy human subjects were equally divided into three groups: non-smokers, cigarette smokers and cannabis smokers. Each group was administered a single dose of sildenafil (50 mg tablets). The primary outcome measures included the maximum concentration of sildenafil in plasma (Cmax), the elimination half-life (t1/2) and the area under the plasma concentration time curve from zero to time (AUC0–t). The pharmacodynamics were assessed by the International Index of Erectile Function (IIEF-5). The exposure of sildenafil (AUC0–t) showed a statistically significant increase in cigarette smokers (1156 ± 542 ng·h/mL) of 61% (p < 0.05) while in cannabis smokers (967 ± 262 ng·h/mL), a non-significant increase in AUC0–t of 35% (p > 0.05) was observed relative to non-smokers (717 ± 311 ng·h/mL). Moreover, the Cmax of sildenafil increased by 63% (p < 0.05) and 22% (p > 0.05) in cigarette smokers and cannabis smokers, respectively. Cigarette smoking increases the exposure of sildenafil to a statistically significant level with no effect on its pharmacodynamics, safety and tolerability.

The inhibitory effect of GLP-1 on food intake is augmented by gastric distension in healthy human subjects

2000 ◽  
Vol 118 (4) ◽  
pp. A74-A75 ◽  
Author(s):  
Daniel Matzinger ◽  
Lukas Degen ◽  
Markus Knupp ◽  
Christoph Beglinger
Keyword(s):  
Food Intake ◽  
Human Subjects ◽  
Inhibitory Effect ◽  
Gastric Distension ◽  
Healthy Human ◽  
Healthy Human Subjects

Long-term facilitation of ventilation is not present during wakefulness in healthy men or women

2002 ◽  
Vol 93 (6) ◽  
pp. 2129-2136 ◽  
Author(s):  
A. S. Jordan ◽  
P. G. Catcheside ◽  
F. J. O'Donoghue ◽  
R. D. McEvoy
Keyword(s):  
Repeated Measures ◽  
Human Subjects ◽  
Minute Ventilation ◽  
Upper Airway ◽  
Menstrual Phase ◽  
Healthy Human ◽  
Dilator Muscle ◽  
Obstructive Sleep ◽  
Long Term Facilitation

Obstructive sleep apnea (OSA) is more common in men than in women for reasons that are unclear. The stability of the respiratory controller has been proposed to be important in OSA pathogenesis and may be involved in the gender difference in prevalence. Repetitive hypoxia elicits a progressive rise in ventilation in animals [long-term facilitation (LTF)]. There is uncertainty whether LTF occurs in humans, but if present it may stabilize respiration and possibly also the upper airway. This study was conducted to determine 1) whether LTF exists during wakefulness in healthy human subjects and, if so, whether it is more pronounced in women than men and 2) whether inspiratory pump and upper airway dilator muscle activities are affected differently by repetitive hypoxia. Twelve healthy young men and ten women in the luteal menstrual phase were fitted with a nasal mask and intramuscular genioglossal EMG (EMGgg) recording electrodes. After 5 min of rest, subjects were exposed to ten 2-min isocapnic hypoxic periods (∼9% O2 in N2, arterial O2 saturation ∼80%) separated by 2 min of room air. Inspired minute ventilation (V˙i) and peak inspiratory EMGgg activity were averaged over 30-s intervals, and respiratory data were compared between genders during and after repetitive hypoxia by using ANOVA for repeated measures. V˙i during recovery from repetitive hypoxia was not different from the resting level and not different between genders. There was no facilitation of EMGgg activity during or after repetitive hypoxia. EMGgg activity was reduced below baseline during recovery from repetitive hypoxia in women. In conclusion, we have found no evidence of LTF of ventilation or upper airway dilator muscle activity in healthy subjects during wakefulness.

Lack of Acipimox-Digoxin Interaction in Patient Volunteers

1992 ◽  
Vol 11 (5) ◽  
pp. 357-359 ◽  
Author(s):  
Chioli Pascal Chijioke ◽  
Richard Martin Pearson ◽  
Strolin Benedetti
Keyword(s):  
Oral Absorption ◽  
Human Subjects ◽  
Plasma Concentrations ◽  
Time Curve ◽  
Digoxin Interaction ◽  
Concentration Time ◽  
Elimination Half ◽  
Significant Difference ◽  
Before And After ◽  
Renal Clearances

1 A study was carried out to find out if digoxin and acipimox interact. 2 Six elderly patients on digoxin were each given acipimox 150 mg three daily for a week, after informed consent. Digoxin and acipimox plasma concentrations and urinary excretion were measured after the first dose of acipimox and after a week of treatment. 3 Data were fitted to a one-compartment oral absorption model. Areas under the plasma concentration-time curve, plasma and renal clearances, and elimination half-life were computed. 4 There was no significant difference in digoxin plasma concentrations and kinetic parameters before and after acipimox administration. Acipimox kinetics were not affected by the concomitant ingestion of digoxin. 5 The patients' clinical condition remained stable during the study. 6 Thus there was no evidence for an adverse interaction between digoxin and acipimox in human subjects under the conditions of this study.

Responses of muscle mass, strength and gene transcripts to long-term heat stress in healthy human subjects

2010 ◽  
Vol 111 (1) ◽  
pp. 17-27 ◽  
Author(s):  
Katsumasa Goto ◽  
Hideshi Oda ◽  
Hidehiko Kondo ◽  
Michihito Igaki ◽  
Atsushi Suzuki ◽  
...  
Keyword(s):  
Heat Stress ◽  
Muscle Mass ◽  
Human Subjects ◽  
Healthy Human ◽  
Healthy Human Subjects ◽  
Gene Transcripts

scholarly journals Playing a P300-based BCI VR game leads to changes in cognitive functions of healthy adults

2020 ◽  
Author(s):  
Matvey Bulat ◽  
Alexandra Karpman ◽  
Alina Samokhina ◽  
Alexander Panov
Keyword(s):  
Virtual Reality ◽  
Cognitive Functions ◽  
Human Subjects ◽  
Healthy Population ◽  
Healthy Human ◽  
Long Term Effect ◽  
New Findings ◽  
Key Points ◽  
Additional Improvement

In this paper, we present the results of a study to determine the effect of the P300-based brain-computer interface (BCI) virtual reality game on the cognitive functions of healthy human subjects. This study is a part of on-going research related to evaluation of the the long-term effect of P300 training in Virtual Reality surrounding (VR game) on the cognitive performance of the young healthy population. A comparison of results between 3 groups of participants (15 people each) revealed the progressing difference in cognitive assessment for experimental group played P300 BCI VR game, showing the positive increase in flanker and conjunction visual search task performance associated with selective attention and mental inhibition. We show that the effect is due to the use of P300 BCI paradigm. Our results suggest that P300 BCI games combined with virtual reality can not only be used for rehabilitation in patients with slight mental disorders or elderly, but for increasing some cognitive functions in healthy subjects, giving an additional improvement in learning in case of combination with possible educational tasks or used for attention trainingGRAPHICAL ABSTRACTPlease check the journal’s author guildines for whether a graphical abstract, key points, new findings, or other items are required for display in the Table of Contents.

Chiral Pharmacokinetics and Metabolite Profile of Prolonged-release Ketamine Tablets in Healthy Human Subjects

2021 ◽  
Author(s):  
Mahmoud Hasan ◽  
Christiane Modess ◽  
Tarek Roustom ◽  
Anne Dokter ◽  
Markus Grube ◽  
...  
Keyword(s):  
Intravenous Infusion ◽  
Human Subjects ◽  
Systemic Exposure ◽  
Metabolite Profile ◽  
Pharmacokinetic Analysis ◽  
Prolonged Release ◽  
Healthy Human ◽  
Time Curve ◽  
Pharmaceutical Dosage Form ◽  
Tandem Mass Spectrometric

Background The anesthetic ketamine after intravenous dosing is nearly completely metabolized to R- and S-stereoisomers of the active norketamine (analgesic, psychoactive) and 2,6-hydroxynorketamine (potential analgesic, antidepressant) as well as the inactive dehydronorketamine. Oral administration favors the formation of 2,6-hydroxynorketamines via extensive presystemic metabolism. The authors hypothesized that plasma exposure to 2,6-hydroxynorketamines relative to the psychoactive ketamine is greater after prolonged-release ketamine tablets than it is after intravenous ketamine. Methods Pharmacokinetics of ketamine after intravenous infusion (5.0 mg) and single-dose administrations of 10, 20, 40, and 80 mg prolonged-released tablets were evaluated in 15 healthy white human subjects by means of a controlled, ascending-dose study. The stereoisomers of ketamine and metabolites were quantified in serum and urine by validated tandem mass-spectrometric assays and evaluated by noncompartmental pharmacokinetic analysis. Results After 40 mg prolonged-release tablets, the mean ± SD area under the concentrations–time curve ratios for 2,6-hydroxynorketamine/ketamine were 18 ± 11 (S-stereoisomers) and 30 ± 16 (R-stereoisomers) compared to 1.7 ± 0.8 and 3.1 ± 1.4 and after intravenous infusion (both P &lt; 0.001). After 10 and 20 mg tablets, the R-ratios were even greater. The distribution volumes at steady state of S- and R-ketamine were 6.6 ± 2.2 and 5.6 ± 2.1 l/kg, terminal half-lives 5.2 ± 3.4 and 6.1 ± 3.1 h, and metabolic clearances 1,620 ± 380 and 1,530 ± 380 ml/min, respectively. Bioavailability of the 40 mg tablets was 15 ± 8 (S-isomer) and 19 ± 10% (R-isomer) and terminal half-life 11 ± 4 and 10 ± 4 h. About 7% of the dose was renally excreted as S-stereoisomers and 17% as R-stereoisomers. Conclusions Prolonged-release ketamine tablets generate a high systemic exposure to 2,6-hydroxynorketamines and might therefore be an efficient and safer pharmaceutical dosage form for treatment of patients with chronic neuropathic pain compared to intravenous infusion. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Effect of clonidine on induced cough and bronchoconstriction in guinea pigs and healthy humans

1994 ◽  
Vol 76 (3) ◽  
pp. 1082-1087 ◽  
Author(s):  
F. O′Connell ◽  
V. E. Thomas ◽  
R. W. Fuller ◽  
N. B. Pride ◽  
J. A. Karlsson
Keyword(s):  
Citric Acid ◽  
Guinea Pigs ◽  
Human Subjects ◽  
Inhibitory Effect ◽  
Healthy Human ◽  
Oral Clonidine ◽  
Healthy Humans ◽  
Human Volunteers ◽  
Dependent Inhibition ◽  
Time To Onset

We examined the effects of the alpha 2-receptor agonist clonidine, administered orally and by inhalation, on citric acid- and capsaicin-induced reflexes in guinea pigs and healthy human subjects. In groups (n = 8-10) of conscious guinea pigs, oral clonidine (10 and 100 micrograms/kg) was without effects, whereas inhaled clonidine (10–1,000 microM) caused a concentration-dependent inhibition of citric acid-induced cough (coughs during 3 min: control, 6.5 +/- 0.9; 1,000 microM clonidine, 1.7 +/- 1.0; P < 0.05) and reflex bronchoconstriction (time to onset of bronchoconstriction: control, 191 +/- 24 s; 1,000 microM clonidine, 317 +/- 33 s; P < 0.05). The inhibitory effect of inhaled clonidine on both reflexes was completely reversed by pretreatment with yohimbine but not with prazosin. In 12 healthy human volunteers, oral clonidine (150 mg) caused a significant fall in supine and erect systolic blood pressure and a significant increase in drowsiness as measured on a visual analogue scale 1 and 2 h after administration. Despite these effects, oral clonidine had no effect on capsaicin-induced cough or reflex bronchoconstriction in humans. In contrast to the effects in guinea pigs, inhaled clonidine (281 microM) had no effect on capsaicin-induced cough or reflex bronchoconstriction in humans. These data suggest that peripheral alpha 2-receptors exert an inhibitory effect on sensory neurotransmission in the guinea pig but not in the healthy human airway, indicating an important difference between the two species.

scholarly journals Caffeine induces gastric acid secretion via bitter taste signaling in gastric parietal cells

2017 ◽  
Vol 114 (30) ◽  
pp. E6260-E6269 ◽  
Author(s):  
Kathrin Ingrid Liszt ◽  
Jakob Peter Ley ◽  
Barbara Lieder ◽  
Maik Behrens ◽  
Verena Stöger ◽  
...  
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Functional Role ◽  
Bitter Taste ◽  
Human Subjects ◽  
Inhibitory Effect ◽  
Healthy Human ◽  
Healthy Human Subjects ◽  
Gastric Parietal Cells

Caffeine, generally known as a stimulant of gastric acid secretion (GAS), is a bitter-tasting compound that activates several taste type 2 bitter receptors (TAS2Rs). TAS2Rs are expressed in the mouth and in several extraoral sites, e.g., in the gastrointestinal tract, in which their functional role still needs to be clarified. We hypothesized that caffeine evokes effects on GAS by activation of oral and gastric TAS2Rs and demonstrate that caffeine, when administered encapsulated, stimulates GAS, whereas oral administration of a caffeine solution delays GAS in healthy human subjects. Correlation analysis of data obtained from ingestion of the caffeine solution revealed an association between the magnitude of the GAS response and the perceived bitterness, suggesting a functional role of oral TAS2Rs in GAS. Expression of TAS2Rs, including cognate TAS2Rs for caffeine, was shown in human gastric epithelial cells of the corpus/fundus and in HGT-1 cells, a model for the study of GAS. In HGT-1 cells, various bitter compounds as well as caffeine stimulated proton secretion, whereby the caffeine-evoked effect was (i) shown to depend on one of its cognate receptor,TAS2R43,and adenylyl cyclase; and (ii) reduced by homoeriodictyol (HED), a known inhibitor of caffeine’s bitter taste. This inhibitory effect of HED on caffeine-induced GAS was verified in healthy human subjects. These findings (i) demonstrate that bitter taste receptors in the stomach and the oral cavity are involved in the regulation of GAS and (ii) suggest that bitter tastants and bitter-masking compounds could be potentially useful therapeutics to regulate gastric pH.

scholarly journals The bright and the dark sides of L-carnitine supplementation: a systematic review

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Angelika K. Sawicka ◽  
Gianluca Renzi ◽  
Robert A. Olek
Keyword(s):  
Systematic Review ◽  
Human Subjects ◽  
Eligibility Criteria ◽  
Healthy Human ◽  
Stress Markers ◽  
Fasting Plasma ◽  
Healthy Human Subjects ◽  
Dose Ranging ◽  
Total Carnitine

Abstract Background L-carnitine (LC) is used as a supplement by recreationally-active, competitive and highly trained athletes. This systematic review aims to evaluate the effect of prolonged LC supplementation on metabolism and metabolic modifications. Methods A literature search was conducted in the MEDLINE (via PubMed) and Web of Science databases from the inception up February 2020. Eligibility criteria included studies on healthy human subjects, treated for at least 12 weeks with LC administered orally, with no drugs or any other multi-ingredient supplements co-ingestion. Results The initial search retrieved 1024 articles, and a total of 11 studies were finally included after applying inclusion and exclusion criteria. All the selected studies were conducted with healthy human subjects, with supplemented dose ranging from 1 g to 4 g per day for either 12 or 24 weeks. LC supplementation, in combination with carbohydrates (CHO) effectively elevated total carnitine content in skeletal muscle. Twenty-four-weeks of LC supplementation did not affect muscle strength in healthy aged women, but significantly increased muscle mass, improved physical effort tolerance and cognitive function in centenarians. LC supplementation was also noted to induce an increase of fasting plasma trimethylamine-N-oxide (TMAO) levels, which was not associated with modification of determined inflammatory nor oxidative stress markers. Conclusion Prolonged LC supplementation in specific conditions may affect physical performance. On the other hand, LC supplementation elevates fasting plasma TMAO, compound supposed to be pro-atherogenic. Therefore, additional studies focusing on long-term supplementation and its longitudinal effect on the cardiovascular system are needed.

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