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Healthy Young Volunteers (healthy + young_volunteer)
Selected AbstractsEvaluation of the cognitive, psychomotor and pharmacokinetic profiles of rupatadine, hydroxyzine and cetirizine, in combination with alcohol, in healthy volunteersHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 1 2006Manuel J. Barbanoj Abstract Introduction The Central Nervous System (CNS) impairment induced by moderate alcohol (ALC) ingestion may be enhanced if other drugs are taken simultaneously. Rupatadine (RUP) is a new H1 -antihistamine which also inhibits platelet activating factor (PAF) release in inflammatory reactions. Objective The main aim of the study was to assess the effects of ALC 0.8,g/Kg on RUP (10,mg and 20,mg) CNS effects. An evaluation of alcohol and RUP pharmacokinetics was also attained. Methods Eighteen healthy young volunteers of both sexes participated in a phase I, randomised, crossover, double-blind, placebo-controlled study. At 2-week intervals they received six treatments: (a) placebo (PLA), (b) ALC alone and ALC in combination with: (c) hydroxyzine 25,mg (HYD), (d) cetirizine 10,mg (CET), (e) RUP 10,mg or (f) RUP 20,mg. At baseline and several times thereafter, seven psychomotor performance tests (finger tapping, fine motoric skills, nystagmus, temporal estimation, critical-flicker-fusion frequency, ,d2' cancellation, simple reaction) and eleven subjective self-reports (drunkenness, sleepiness, alertness, clumsiness, anger, inattentiveness, efficiency, happiness, hostility, interest and extraversion) were carried out. Two-way (treatment, time) ANOVAs for repeated measures to each variable together with a multivariate non-parametric approach were applied. Plasma concentrations of alcohol, and of RUP and its metabolites, were quantified by validated immunofluorescence and LC/MS/MS methods, respectively. Plasma-time curves for all compounds were analysed by means of model-independent methods. Results The combination of alcohol with HYD, CET and RUP 20,mg produced more cognitive and psychomotor impairment as compared to alcohol alone, being the combination of alcohol and HYD the one which induced the greatest deterioration. The combination of alcohol and RUP 10,mg could not be differentiated from ALC alone. Subjective self-reports reflect effects on metacognition after the combination of alcohol with HYD and CET i.e. the increased objective impairment observed was not subjectively perceived by the subjects. No significant differences were obtained when comparing alcohol plasma concentrations assessed after the treatments evaluated. RUP showed a lineal kinetic relationship after 10 and 20,mg with a higher exposition to both metabolites assayed. Conclusions Present results showed that single oral doses of rupatadine 10,mg in combination with alcohol do not produce more cognitive and psychomotor impairment than alcohol alone. Higher doses of rupatadine, in combination with alcohol, may induce cognitive and psychomotor deterioration as hydroxyzine and cetirizine at therapeutic doses. Copyright © 2006 John Wiley & Sons, Ltd. [source] Interactions between alcohol and caffeine in relation to psychomotor speed and accuracyHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 3 2002Michelle Mackay Abstract Unlike other CNS depressants, alcohol intoxication can be associated with increased error rates, coupled with unaffected (or speeded) response rates during psychomotor and cognitive processing. The present study examined whether concurrent consumption of caffeine may differentially affect these aspects of alcohol and performance. A randomised, double-blind, placebo-controlled design was utilised in which 64 healthy young volunteers received either 0.66,g/kg alcohol, caffeine (110,120,mg), both or neither. Performance was assessed using a four choice reaction time task (FCRT) with elements of repetitive (predictable) and random stimuli sequences and the digit symbol substitution task (DSST). Individuals on alcohol made significantly more errors during both fixed and random FCRT sequences, and there was evidence of weak antagonism of these effects by caffeine on the latter measure. On the DSST test of psychomotor speed, alcohol was associated with a significant slowing, the caffeine group were significantly faster and there was clear antagonism of the effects of alcohol by caffeine. These findings confirm that alcohol consumption is associated a greater number of errors and provide some evidence for task-specific antagonism of alcohol's cognitive effects by caffeine. Copyright © 2002 John Wiley & Sons, Ltd. [source] Smoking behaviour modulates pharmacokinetics of orally administered clopidogrelJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2008A.-M. Yousef PhD Summary Background and objectives:, Clopidogrel is an important antiplatelet drug that is effective in preventing thrombotic events, especially for patients undergoing percutaneous coronary intervention. The therapeutic usefulness of clopidogrel has been limited by documented inter-individual heterogeneity in platelet inhibition, which may be attributable to known clopidogrel pharmacokinetic variability. The objective of this study was to assess the influence of smoking cigarettes and abnormal body weight on the pharmacokinetics of clopidogrel. Methods:, Seventy-six healthy adult male volunteers were selected randomly. Each subject received a single 75 mg oral dose of clopidogrel after overnight fast. Clopidogrel carboxylate plasma levels were measured and non-compartmental analysis was used to determine peak plasma concentration (Cmax), time to peak plasma concentration (Tmax), elimination half-life (t1/2e), and area under the curve (AUC0,,). Results:, One-third of volunteers were smokers (n = 27) and one-half had abnormal body weight (n = 39). Smokers had lower AUC0,, (smokers: 6·24 ± 2·32 ,g/h/mL vs. non-smokers: 8·93 ± 3·80 ,g/h/mL, P < 0·001) and shorter half-life (smokers: 5·46 ± 2·99 vs. non-smokers: 8·43 ± 4·26, P = 0·001). Smoking behaviour had no influence on Cmax (P = 0·3) and Tmax (P = 0·7). There was no statistically significant difference in Cmax, AUC0,,, Tmax and t1/2e between volunteers with abnormal body weight and normal body weight. However the difference in body weight of the two groups was relatively narrow (mean ± SE; 26·93 ± 0·16 vs. 23·11 ± 0·27). In general, the pharmacokinetic parameters were characterized by considerable inter-individual differences (Cmax = 3·09 ± 0·99 ,g/mL, CV = 32%), (Tmax =0·76 ± 0·24 h, CV = 31·6%), (AUC0,, = 7·98 ± 3·58 ,g/h/mL, CV = 44·8%), and (t1/2e = 7·38 ± 4·10 h, CV = 55·6%). Conclusion:, Smoking is a significant factor affecting the pharmacokinetics of clopidogrel, following administration of a single 75 mg dose in healthy young volunteers. The study supports smoking-cessation recommendations. Further studies are required to evaluate the influence of smoking and body weight on the pharmacokinetics of the active metabolite of clopidogrel and on the clinical effects of any differences observed. [source] Acute Effects of Low Doses of Red Wine on Cardiac Conduction and Repolarization in Young Healthy SubjectsALCOHOLISM, Issue 12 2009Matteo Cameli Background:, Moderate to high blood concentrations of ethanol have been shown to yield acute changes in cardiac electrophysiological properties, but the effect of low concentrations have never been assessed. The role of concomitant changes in clinical variables or cardiac dimensions is also still unknown. This study aimed at exploring the acute effects of low doses of ethanol, administered as Italian red wine, on conduction, depolarization, and repolarization electrocardiographic (ECG) intervals in a population of healthy subjects. Methods:, Forty healthy young volunteers drank a low quantity of red wine (5 ml/kg), and an equal volume of fruit juice in separate experiments. Heart rate, P-wave duration, PR interval, QRS duration, QT interval, corrected QT interval, QT dispersion, and corrected QT dispersion were assessed at baseline and after 60 minutes from challenge. Results:, Mean blood ethanol concentration after drinking was 0.48 ± 0.06 g/l. Compared to the control challenge, significant changes after red wine intake were observed in P-wave duration (from 101 ± 11 to 108 ± 14 milliseconds, p = 0.0006), PR interval (from 153 ± 15 to 167 ± 17 milliseconds, p < 0.0001), QT interval (from 346 ± 28 to 361 ± 24 milliseconds, p < 0.0001), and corrected QT interval (from 388 ± 24 to 402 ± 30 milliseconds, p = 0.0006). None of these changes showed correlations with modifications in clinical or echocardiographic variables. In multivariate analyses aimed at exploring predictors of ECG changes, none of the variables entered the final models. Conclusions:, Low doses of red wine acutely slow cardiac conduction and prolong repolarization in normal individuals. These changes are poorly predictable. The potential arrhythmogenic impact of these effects is worthy of exploration. [source] Human duodenal phase III migrating motor complex activity is predominantly antegrade, as revealed by high-resolution manometry and colour pressure plotsNEUROGASTROENTEROLOGY & MOTILITY, Issue 4 2002J. M. Andrews Abstract,Late phase III migrating motor complex activity has been said to be primarily retroperistaltic but has not been assessed with high resolution manometry or three-dimensional colour pressure plots (pressure/time/distance). Duodenal phase III was examined in healthy young volunteers (seven male, two female) with a 20-lumen assembly. With the most proximal sidehole in the distal antrum, after a 4.5-cm interval 18 sideholes at 1.5-cm intervals spanned the duodenum with a final sidehole 3 cm beyond. Fasting pressures were recorded until phase III occurred. Comparisons were made between proximal (P) and distal (D) duodenum during early (E) (first 0.5,1 min) and late (L) (last 0.5,1 min) phase III. With colour pressure analysis, 121 of 180 pressure wave (PW) sequences were purely antegrade, two purely retrograde and 57 bidirectional. Ten of fifty-seven bidirectional PW sequences were complex, branching to become two separate sequences. Bidirectional sequences occurred more frequently in late than early phase III (L 43 vs. E 14 of 57), but their occurrence did not differ between proximal and distal duodenum (P31 vs. D 24 of 57). Antegrade propagation velocity was faster in late compared with early phase III (L 28.50 vs. E 17.05 mm s,1; P = 0.006), but did not differ between proximal and distal duodenum. Colour pressure analysis also indicated an intermittent segmental pattern to phase III, with each subject exhibiting a change in velocity or direction, or a relative failure of peristalsis somewhere along the duodenum during part of phase III. Duodenal phase III is not homogenous and, in contrast with previous studies, does not primarily constitute a retroperistaltic pump. Colour pressure analysis is useful in interpreting intraluminal pressure profiles and may improve the sensitivity and specificity of clinical studies. [source] Brain potentials associated with the onset and offset of rapid eye movement (REM) during REM sleepPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 3 2002KEIKO OGAWA Abstract The relationship between dreaming and rapid eye movements (REM) during REM sleep is still controversial. This study records the brain potentials time-locked to the onset and offset of REM in 11 healthy young volunteers. Before the onset of REM, no presaccadic readiness potential was found. Conversely, two positive potentials (P1 and P2) appeared following the offset of REM. The latter potentials were dominant in the parieto-occipital area. These findings suggest that REM is initiated without preparation but elicits some information-processing activities that were speculated to occur in the cortical visual area. The data support the activation,synthesis or association hypothesis of dreaming rather than the scanning hypothesis. [source] Deterioration of the Pharyngo-UES Contractile Reflex in the Elderly ,THE LARYNGOSCOPE, Issue 9 2000Junlong Ren MD Abstract Objectives/Hypothesis Deterioration of aerodigestive tract reflexes such as the esophagoglottal and pharyngoglottal closure reflexes and pharyngeal swallow has been documented in the elderly. However, the effect of aging on the contractile response of the upper esophageal sphincter (UES) to pharyngeal water stimulation has not been studied. The aim of this study was to characterize the pharyngo-UES reflex in the healthy elderly. Methods We studied nine healthy elderly (77 ± 1 y [SD]; four men, five women) and nine healthy young volunteers (26 ± 2 y [SD]; four men, five women). A UES sleeve sensor was used to measure the pressure. We tested pharyngeal stimulation induced by rapid pulse and slow continuous injection of water. Results The volume of water required to stimulate the pharyngo-UES contractile reflex by rapid pulse injection in the elderly (0.5 ± 34 0.1 mL) was significantly higher than that in the young (0.1 ± 0.02 mL) (P < .05). In contrast to young subjects, there was no pressure increase in resting UES pressure observed in the elderly for continuous pharyngeal water infusion. In both young and elderly, the threshold volume for the pharyngo-UES contractile reflex was significantly lower than that for pharyngeal swallows. Conclusions The pharyngo-UES contractile reflex deteriorates with aging. This deterioration is primarily due to abnormalities of the afferent limb of the reflex. [source] | ||||||||||