Parameters In Healthy Volunteers Research Articles

Assessment of corticospinal tract (CST) damage in acute stroke patients: Comparison of tract‐specific analysis versus segmentation of a CST template

To compare two techniques to assess corticospinal tract (CST) damage in stroke patients: tract-specific analysis by probabilistic tractography and segmentation using a CST template. We extracted fractional anisotropy (FA) values, the FA ratio, and mean diffusivity (MD) in 18 stroke patients and 21 healthy volunteers matched for age and sex. We compared the two methods in order to determine their ability to detect 1) differences between diffusion tensor imaging (DTI) parameters of healthy volunteers and stroke patients, 2) the correlation between DTI parameters and clinical scores, and 3) the correlation between DTI parameters and blood oxygen level-dependent (BOLD) signals in a fist-closure task. FA values were higher with the tractography approach than with the segmentation method, but differences between the ipsilesional CST and the homologous region in healthy subjects were detected using both methods. In patients, clinical scores were significantly correlated with FA values and FA ratios with both methods. The BOLD signal was positively correlated with FA values for CST with the segmentation but not with the tractography approach. CST damage in stroke patients can be assessed by either probabilistic tractography or segmentation of a CST template. Although each method has advantages and limitations, both are sensitive enough to detect differences among stroke patients and identify specific correlations with clinical scores.

Variables associated with corneal confocal microscopy parameters in healthy volunteers: implications for diabetic neuropathy screening

Corneal confocal microscopy is a promising screening method for diabetic neuropathy. Although much research in this field has been accomplished, we aimed to determine and confirm the known clinical and eyewear variables associated with the parameters of corneal confocal microscopy specifically in healthy volunteers, in particular associations with corneal nerve fibre length. Clinical characteristics, electrophysiological examination and a general clinical eye history were collected from 64 healthy volunteers. Corneal confocal microscopy was performed to determine corneal nerve fibre length, corneal nerve branch density, corneal nerve fibre density and tortuosity coefficient. Univariate and multivariate linear regression analysis was used to determine clinical variables associated with corneal nerve fibre length parameters. We observed that corneal nerve fibre length has a broad distribution in healthy volunteers (18 ± 4 mm/mm(2), 95% confidence interval, 12.3-25.7 mm/mm(2)). Multivariate regression analysis demonstrated that HbA(1c) was the only independent clinical factor to account for variations in corneal nerve fibre length, independent of age and status of contact lens wear. This study does not provide convincing evidence that corneal nerve fibre length is independently associated with age or the wearing of contact lenses, and that these factors are therefore unlikely to hinder valid screening for polyneuropathies such as diabetic neuropathy. Furthermore, the strong inverse association of corneal nerve fibre length with glycaemic exposure may support the use of this parameter to detect subclinical pre-diabetic nerve injury.

Dose findings of antofloxacin hydrochloride for treating bacterial infections in an early clinical trial using PK-PD parameters in healthy volunteers

To find an appropriate dose regimen of the novel antibacterial agent antofloxacin for a phase II clinical trial using a population pharmacokinetic (PPK) study in healthy volunteers and the minimum inhibitory concentration (MIC) as pharmacodynamic (PD) parameters. Twenty-four healthy volunteers were enrolled in a double-blind crossover study and received antofloxacin (200 or 400 mg/d, po) for consecutive 5 d with 10 d washout between two separate periods. Blood concentrations were analyzed using HPLC with a UV-Vis detector. The values of area under the curve (AUC) with covariates were obtained from a PPK model, and the MICs came from the previous in vitro studies. The dose regimen was determined for the phase II clinical trial according to the ratio (>20) of AUC/MIC, and the efficacy of the dose was evaluated by the trial. A two-compartment model best described the time-concentration data with first-order absorption. The PPK parameter estimates for CL, V(c), Q, V(p) and K(A) are 8.34 L/h, 142 L, 15.9 L/h, 52.2 L and 4.64 1/h, respectively. The covariates sex for K(A), weight for CL, weight for V(c) and interoccasion variability were included in the final model. The AUC/MIC was calculated based on the PPK model and the MIC of antofloxacin for Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus and Staphylococcus epidermidis were determined in previous researches. The 400 mg loading dose with 200 mg/d maintenance dose was recommended and confirmed by the phase II trial. The ratio of AUC from the PPK model vs MIC as the PD parameter can be applied in a dose-finding trial of antofloxacin in treatment of bacterial infections. The PPK model suggests that sex and body weight may be considerations in regards to individual therapy, which should be investigated in larger clinical trials and serve as a potential reference for clinical therapies.

Oxytocin interference in the effects induced by inhalation of 7.5% CO2 in healthy volunteers

The objective of this study was to assess the acute effect of intranasally administered oxytocin (OT) on subjective states, cardiovascular, and endocrine parameters in healthy volunteers who inhaled 7.5% CO(2) . Forty-five subjects were allocated into three matched groups of subjects who received 24 international units (IU) of OT, 2 mg of lorazepam (LZP), or placebo (PL). The challenge consisted of medical air inhalation for 20 min, 10 min of rest, and CO(2) 7.5% inhalation for 20 min. Subjective effects were evaluated by self-assessment scales; heart rate, blood pressure, skin conductance, and salivary cortisol were also measured. Assessments were performed at four time points: (i) baseline (-15 min); (ii) post-air inhalation (90 min); (iii) post-CO(2) inhalation (120 min), and (iv) post-test (160 min). CO(2) inhalation significantly increased the anxiety score in the PL group compared with the post-air measurement but not in the OT or LZP groups. The LZP reduced anxiety after medical air inhalation. Other parameters evaluated were not affected by OT. OT, as well as LZP, prevented CO(2) -induced anxiety, suggesting that this hormone has anxiolytic properties.

Extrafine Beclometasone Dipropionate and Formoterol in Single and Separate Inhalers

The aim of this study was to evaluate the pharmacokinetics and pharmacodynamics of single administration of extrafine beclometasone (BDP)/formoterol hydrofluoroalkane (HFA) (Foster®, Chiesi Farmaceutici S.p.A., Italy) by pressurized metered dose inhaler (pMDI) in healthy volunteers, compared to the free combination of extrafine BDP pMDI (QVAR®, 3 M) and extrafine formoterol pMDI (Atimos®, Chiesi Farmaceutici S.p.A.) delivered via separate inhalers. Twelve healthy male volunteers completed this open label, randomized, single-dose, placebo-controlled, threeway cross-over study. Volunteers received (i) 4 inhalations of the fixed-combination of BDP/formoterol HFA (100/6 μg), (ii) 4 inhalations of BDP HFA (100 μg) and 2 inhalations of formoterol HFA (12 μg) administered separately or (iii) 4 inhalations of placebo HFA. There was a 7-day washout between treatment periods. PK parameters of BDP, FF, and of the main BDP metabolite (B17MP) were calculated. The systemic exposure to B17MP and formoterol after administration as a fixed combination or via separate inhalers was comparable. For B17MP, Cmax (794 ± 316 vs 663 ± 329 pg/mL), AUC0-t (3076 ± 1102 vs 2773 ± 833 pg.h/mL) and AUC0-30min (296 ± 11.7 vs 230 ± 13.3 pg.h/mL) were slightly higher, but not statistically significant, with the fixed than with the free combination. For formoterol, neither Cmax (27.6 ± 12.2 vs 28.7 ± 16.3 pg/mL) nor AUC0-t (69.3 ± 28.5 vs 67.4 ± 28.7 pg.h/mL) were significantly different between fixed and free combination. There was also no significant difference between the two combinations in serum cortisol levels, or cortisol urinary excretion adjusted for creatinine. Use of a single inhaler rather than separate inhalers to deliver extrafine drug particles of both BDP and formoterol to the lung does not modify relevant pharmacokinetics and pharmacodynamic parameters in healthy volunteers, therefore it may be considered as a therapeutic option to improve compliance in asthma patients who need chronic treatment.

Investigation of the Effect of Ambient Temperature and Geomagnetic Activity on the Vascular Parameters of Healthy Volunteers

Aim of this paper is to reveal whether the geomagnetic activity (GMA) and meteorological factors (MFs) affect vascular parameters of healthy volunteers. As a trial study we used new device “Tonocard,” and new vascular parameters for study—a pulse wave velocity (PWV) and an endothelial function (EnF) in addition to blood pressure measurements. These parameters never investigated before in such aspects. As far as novelty of device itself and investigated parameters we limited ourselves by monitoring only four healthy volunteers (without cardiovascular pathology). To analyze the sensitivity of their aforementioned medical indices to GMA and MFs two independent mathematical approaches were used, one of whom is based on traditional methods of mathematical statistics and the other on the theory of pattern recognition Dependence of physiological characteristics on the atmospheric temperature, revealed by both applied mathematical approaches, showed complex non-linear character of biological replies: the reaction has a different form in different temperature ranges and is manifested in the form of synchronization of slow variations of physiological and atmospheric parameters (trends) with a period of several days, while the daily variations were virtually independent. The systolic blood pressure (SBP), PWV and a difference between two specially selected values of PWV (DPWV) are approximately equally depending on atmospheric temperature, which accounts for an average of 26% to 28% of their variations. Sensitivity to the GMA for this test was found only for PWV.

Prucalopride

Prucalopride, a first-in-class dihydrobenzofuran-carboxamide derivative, is a potent, selective and specific serotonin 5-HT(4) receptor agonist with enterokinetic properties. Over a 12-week treatment period, prucalopride 2 and 4 mg once daily significantly improved bowel habit assessments (based on patient diary data) relative to placebo in three large, randomized, double-blind, multicentre trials in patients (aged 17-95 years) with severe chronic constipation, the majority of whom were women who experienced inadequate relief with previous therapies. There was no additional benefit with the 4 mg/day over the 2 mg/day dosage of prucalopride. Patient assessments of constipation symptoms and severity, treatment efficacy, satisfaction with bowel habit and treatment, and health-related quality of life were also significantly improved with prucalopride compared with placebo. The improvement in patient satisfaction with bowel habit and treatment was maintained for up to 24 months in open-label, multicentre, long-term follow-up studies. Prucalopride therapy was generally well tolerated; most adverse events in the 12-week studies were transient and of mild to moderate severity. In terms of cardiovascular tolerability, the incidence of QT interval prolongation with prucalopride at dosages of 2 and 4 mg/day was low and similar to that with placebo. Moreover, prucalopride at dosages up to 20 mg/day (10-fold higher than the recommended therapeutic dosage) had no clinically relevant effects on cardiovascular parameters in healthy volunteers.

Effects of acute and subacute garlic supplement administration on serum total antioxidant capacity and lipid parameters in healthy volunteers

Garlic has long been used for medicinal purposes. It has been shown that different forms of garlic have significant antioxidant effects. The strong flavor, odor and unwanted gastrointestinal side effects of fresh garlic has rendered the use of commercial garlic supplements as a preferable option. To investigate the effects of garlic supplementation on serum total antioxidant capacity and lipid parameters, 17 healthy volunteers were administered four standardized commercial garlic tablets every day for 30 days. Blood samples were taken at day 1 (before the first administration of tablets [control] and at 3 h after the administration of tablets), 15 and 30 days, respectively. Total antioxidant capacity (TAC), total cholesterol, low density lipoprotein cholesterol (LDL cholesterol), high density lipoprotein cholesterol (HDL cholesterol) and triglyceride (TG) were measured in sera. Serum TAC was increased significantly at 30 days compared with 15 days, 3 h and control. There was also a significant increase in serum TAC at 15 days compared with 3 h and control. Total cholesterol, LDL cholesterol, HDL cholesterol and TG were not found to be significantly different between control, 3 h, 15 and 30 days. These data suggest that garlic, used as a dietary supplementation, may be beneficial in increasing the antioxidant capacity of the body.

Regulatory effects of a fermented food concentrate on immune function parameters in healthy volunteers

Objective Nutrition is known to influence the immune system and can thereby modulate resistance to infection. The objective of this clinical trial was to assess the influence of a cascade-fermented food consisting of fruits, nuts, and vegetables rich in polyphenols (Regulat) on the immune system in healthy volunteers. Methods The clinical trial was double-blinded and placebo-controlled. In total, 48 healthy men 20–48 y of age with a body mass index of 20–28 kg/m 2 were enrolled in the clinical trial. The group was characterized according to lifestyle parameters and only men with regular low to moderate intake of fruit and vegetables were enrolled. The intervention lasted for a period of 4 wk. Volunteers received Regulat twice daily or a placebo product (essence of vinegar). Results The intake of Regulat significantly enhanced intracellular glutathione content in lymphocytes ( P < 0.05), monocytes ( P < 0.05), and natural killer cells ( P < 0.01). Furthermore, activation of natural killer cell cytotoxicity in response to interleukin-2 stimulation ( P < 0.05), a reduction of total lipid peroxidation, and a reduction of soluble vascular cell adhesion molecule-1 ( P < 0.01) and soluble intercellular adhesion molecule-1 ( P < 0.05) as inflammatory blood markers were found in the Regulat but not in the placebo group. Conclusion In summary, the results from this intervention study demonstrate promising physiologic effects of immune regulation on the innate immune system and antioxidative and anti-inflammatory parameters after Regulat supplementation. However, these promising results need to be confirmed in more volunteers with a more prolonged application to ensure significant beneficial effects of Regulat in the general population.

Effects of polydextrose supplementation on different faecal parameters in healthy volunteers

Polydextrose (PDX) is a non-digestible polysaccharide providing beneficial effects on bowel health. The aim of the study was to show prebiotic effects of PDX. A placebo-controlled, randomized intervention study with PDX supplementation (8 g/day) was conducted in 45 healthy subjects. The effects of PDX on stool weight, orofaecal transit time, consistency of stool (Bristol stool form scale), short-chain fatty acid production, pH value, neutral sterol and bile acid excretion and faecal microbiota were evaluated. It was found that supplementation of PDX shortened the orofaecal transit time significantly. Furthermore, ingestion of PDX resulted in a decreased pH value and in significant changes in bile acid and neutral sterol excretion. PDX had no effects on stool weight, concentrations of the abundant short-chain fatty acids (acetate, propionate) and faecal contents of Lactobacillus acidophilus and Bifidobacterium lactis. In conclusion, PDX is able to shorten the orofaecal transit time and to improve stool consistency in subjects suffering from constipation.

Pharmacokinetics of Lofexidine Hydrochloride in Healthy Volunteers

The objective of this study was to characterize the clinical pharmacokinetic profile of lofexidine after oral delivery. A single dose, cross-over study and a multidose study using healthy volunteers were conducted for that purpose. In the single dose study the average time to maximum concentration was observed at approximately 3h for the single doses tested (1.2mg dose and 2.0mg). Area under the curve from time zero to infinity (AUC0−∞) demonstrated a degree of dose proportionality with a 1.72-fold increase as the dose increased by a factor of 1.67. Elimination rates and terminal half-lives were comparable between dose levels. The average elimination rates for the 1.2mg and the 2.0mg doses were 0.063 and 0.065h−1, respectively. In the multidose study, the average maximum concentration observed after the first dose of 0.4mg was 433 ng/L and ranged from 338 to 586 ng/L. This was slightly lower in proportion to the maximum concentration observed in the single dose study where Cmax was 1755 ng/L at the 1.2mg dose (normalized to 585 ng/L for 0.4mg dose) and for the 2.0mg dose (normalized to 559 ng/L for 0.4mg dose). The average time to maximum concentration (Tmax) was 3.33h which is comparable to values observed in the single dose study. The pharmacokinetic data indicate that lofexidine has a consistent profile. Steady state seems to be reached after 2 days on lofexidine, which is consistent with the lofexidine elimination half-life of approximately 11h. Evaluation of the Tmax, elimination rate, and terminal half-life are consistent across all dose levels studied, suggesting that changing the dose does not affect the absorption or elimination rates of lofexidine HCl. Thus, although preliminary due to the limited number of subjects, these findings are the first to document lofexidine clinical pharmacokinetic parameters in healthy volunteers using a highly sensitive liquid chromatography tandem mass spectrometric analysis. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:319–326, 2009

The effect of experimentally induced psychological stress on seminal parameters in healthy volunteers

Studies on the effects of psychological stress on maleinfertility have so far yielded equivocal findings [1,2]. Themajority of these studies were based on subjective assess-ments of chronic stress. The aim of this study was to deter-mine the effect of experimentally induced acute stress onseminal parameters.

The effect of mastication on occlusal parameters in healthy volunteers

To assess possible associations between occlusal parameters and comminution of solid food during chewing in a group of completely dentate subjects. Twenty-five completely dentate volunteers (28 teeth, 14 functional dental units) aged 24-50 yrs, without any complaints of the stomatognathic system participated in this study. An Optosil test was used to estimate masticatory efficiency for 20 and 80 cycles of chewing. An occlusal analysis, using the T-Scan II System, was performed to assess the following occlusal parameters: the distribution of occlusal contacts, the time of occlusion, the chewing platform area before chewing and after 20 and 80 cycles of chewing. The parameters, that were taken into account: i. X50 for 20 and 80 cycles of chewing, ii. the occlusion time, iii. the occlusal contact area. The occlusion time decreased after 20 and 80 chewing cycles (mean TO0=0.28+/-0.07 vs TO20=0.21+/-0.05 s vs TO80=0.18+/-0.05 s, respectively). The mean value of the chewing platform area was 125.12+/-46.5 mm2. Prolongation of chewing produces, shortening of the occlusion time while the chewing platform area remains at the same level independent of the number of chewing cycles.

The Influence of the Call with a Mobile Phone on Heart Rate Variability Parameters in Healthy Volunteers

It is possible that electromagnetic field (EMF) generated by mobile phones (MP) may have an influence on the autonomic nervous system (ANS) and modulates the function of circulatory system. The aim of the study was to estimate the influence of the call with a mobile phone on heart rate variability (HRV) in young healthy people. The time and frequency domain HRV analyses were performed to assess the changes in sympathovagal balance in a group of 32 healthy students with normal electrocardiogram (ECG) and echocardiogram at rest. The frequency domain variables were computed: ultra low frequency (ULF) power, very low frequency (VLF) power, low frequency (LF) power, high frequency (HF) power and LF/HF ratio was determined. ECG Holter monitoring was recorded in standardized conditions: from 08:00 to 09:00 in the morning in a sitting position, within 20 min periods: before the telephone call (period I), during the call with use of mobile phone (period II), and after the telephone call (period III). During 20 min call with a mobile phone time domain parameters such as standard deviation of all normal sinus RR intervals (SDNN [ms]--period I: 73.94+/-25.02, period II: 91.63+/-35.99, period III: 75.06+/-27.62; I-II: p<0.05, II-III: p<0.05) and standard deviation of the averaged normal sinus RR intervals for all 5-mm segments (SDANN [ms]--period I: 47.78+/-22.69, period II: 60.72+/-27.55, period III: 47.12+/-23.21; I-II: p<0.05, II-III: p<0.05) were significantly increased. As well as very low frequency (VLF [ms2]--period I: 456.62+/-214.13, period II: 566.84+/-216.99, period III: 477.43+/-203.94; I-II: p<0.05), low frequency (LF [ms(2)]--period I: 607.97+/-201.33, period II: 758.28+/-307.90, period III: 627.09+/-220.33; I-II: p<0.01, II-III: p<0.05) and high frequency (HF [ms(2)]--period I: 538.44+/-290.63, period II: 730.31+/-445.78, period III: 590.94+/-301.64; I-II: p<0.05) components were the highest and the LF/HF ratio (period I: 1.48+/-0.38, period II: 1.16+/-0.35, period III: 1.46+/-0.40; I-II: p<0.05, II-III: p<0.05) was the lowest during a call with a mobile phone. The tone of the parasympathetic system measured indirectly by analysis of heart rate variability was increased while sympathetic tone was lowered during the call with use of a mobile phone. It was shown that the call with a mobile phone may change the autonomic balance in healthy subjects. Changes in heart rate variability during the call with a mobile phone could be affected by electromagnetic field but the influence of speaking cannot be excluded.

Effects of a Pneumatic Tube System on Routine and Novel Hematology and Coagulation Parameters in Healthy Volunteers

Effects of a Pneumatic Tube System on Routine and Novel Hematology and Coagulation Parameters in Healthy Volunteers

Bilateral ce-MR angiography of the hands at 3.0 T and 1.5 T: intraindividual comparison of quantitative and qualitative image parameters in healthy volunteers

The purpose of this study was to determine the benefit of bilateral contrast-enhanced MR angiography (ce-MRA) of the hands at 3.0 Tesla (T) compared with an established 1.5-T technique in healthy volunteers. Intraindividual bilateral ce-MRA of the hands was performed at 1.5 T and 3.0 T in 14 healthy volunteers using a timed ultra-fast GRE sequence featuring parallel acquisition. The evaluation comprised measurement of the vessel signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), rating of the image quality and the assessment of artefacts and venous contamination. At 3.0 T, SNR improved up to 95% and CNR up to 129%. The image quality of the larger inflow arteries, the palm arches and common digital arteries was good or sufficient at either magnetic field strengths. However, 3.0-T MRA was clearly superior in the depiction of the digital arteries. Ce-MRA of the hand clearly profits from the use of 3.0 T. Compared with 1.5 T, a substantial increase of CNR is found resulting in a significantly better delineation of the small digital arteries. Saturation affects more the SNR of the perivascular tissue than the contrast-enhanced blood, and thus leads to a marked increase of CNR at 3.0.

Abstract 3661: “Energy Drink” Consumption Causes Increases in Blood Pressure and Heart Rate

Introduction: “Energy drinks” are very popular and are used frequently, especially by young adults. Most marketed energy drinks contain high levels of caffeine and taurine. Both caffeine and taurine have been shown to have direct effects on cardiac function and hemodynamic status. Hypothesis: We assessed the hypothesis that a commonly used energy drink alters blood pressure, heart rate and EKG parameters in healthy volunteers. Methods: Healthy volunteers (n = 15, 53% female, 25.9 ± 5.9 years, 69.8 ± 14.8 kg) abstained from caffeine for 48 hours prior to and throughout the study period. On study day 1 (D1), blood pressure (BP), heart rate (HR) and an EKG were measured at baseline. Participants then consumed 500 mL (2 cans) of an energy drink containing caffeine (80 mg) and taurine (1000 mg) and BP, HR and EKG measurements were repeated at 30 minutes, 1, 2, 3, and 4 hours after consumption. Participants then consumed 2 cans of energy drink daily for the next 5 days (D2–D6). On day 7 (D7) the procedures followed on D1 were repeated. Average baseline measurements on days 1 and 7 were compared to maximum values during that observation period. Results: On both D1 and D7, maximum mean systolic BP, HR and corrected QT-interval (QTc) occurred at 4 hours. Maximum diastolic BP occurred at 2 hours on D1 and D7. Baseline and maximum mean values are presented in Table 1 . Within 4 hours of energy drink consumption on D1 and D7 respectively, systolic BP increased by 7.9% (p = 0.006) and 9.6% (p &lt; 0.001), HR increased by 7.8% (p = 0.009) and 11.0% (p &lt; 0.001) and QTc increased by 4.5% (p = 0.368) and 5.5% (p = 0.052). Diastolic BP increased by 7.0% (p = 0.046) and 7.8% (p = 0.063) within 2 hours of energy drink consumption. Conclusions: In conclusion, although no significant EKG changes were observed, subjects’ HR increased 5–7 bpm and systolic BP increased 10mmHg after consuming an “energy drink”. This level of change is likely clinically significant in patients with cardiac disease or those who consume such drinks regularly. Table 1. Baseline and Maximum Values (mean ± SD)

Changes in haemocoagulation in healthy volunteers after a 1-hour thrombotripsy using a diagnostic 2–4 MHz transcranial probe

The aim was to monitor the changes in haemocoagulation parameters in healthy volunteers after a thrombotripsy with 1-hour transcranial Doppler monitoring using a 2-4 MHz probe. About 10 healthy volunteers underwent a 1-hour thrombotripsy of the middle cerebral artery (MCA), thrombotripsy of the radial artery and a standard 20-min neurosonologic examination (NSE) in 2-week intervals. Platelet count, aPTT, prothrombin time, fibrinogen, D-dimers, tPA, FDP, alpha-2-antiplasmin (AP), plasminogen, PAI-1 antigen, time of euglobulin clot lysis (ECL), homocysteine, and lipoprotein (a) were examined before, at the end and 24 h after a thrombotripsy. All adverse events were monitored. After a thrombotripsy of the MCA, PAI-1 antigen, tPA antigen, fibrinogen and AP activity were significantly decreased by a mean of 32, 23, 7, and 4% respectively (P < 0.05 in all cases). After a thrombotripsy of the RA, there was a significant decrease in tPA antigen alone by an average of 14% (P < 0.05). Standard NSE did not affect any of the measured factors. Thrombotripsy with 1-hour TCD monitoring using a 2-4 MHz diagnostic probe may affect the fibrinolytic system in humans.

Retrospective analysis of electrocardiographic changes after administration of oral or intravenous garenoxacin in five phase I, placebo-controlled studies in healthy volunteers

Certain fluoroquinolones and macrolide antibiotics have been associated with prolongation of the corrected QT (QTc) interval or QT dispersion, leading to cardiac arrhythmias. Garenoxacin is a des-F(6)-quinolone with broad-spectrum antimicrobial activity and a favorable pharmacokinetic/pharmacodynamic profile. Its effects on electrocardiographic (ECG) parameters in healthy volunteers have not been reported. The cardiac safety profile of garenoxacin was further examined using data from healthy volunteers enrolled in 5 dose-ranging and comparative Phase I clinical studies. This was a retrospective analysis of 5 randomized, double-blind, placebo-controlled studies in which 224 healthy volunteers received oral or intravenous garenoxacin (50-1200 mg/d) for 1 to 28 days' dosing duration (<or=14 days' therapeutic duration). The effects of garenoxacin on the QT interval corrected using Bazett's formula (QTcB) and Fridericia's formula (QTcF) and the PR interval were assessed by counts of outliers, linear regressions, and exposure-response plots. Absence of a concentration-dependent effect of garenoxacin on changes from baseline ECG parameters was concluded if the 95% CI for the linear regression slopes of derived QTc- or PR-interval parameters relative to Cmax and C(avg0-12) (average garenoxacin plasma concentration from 0-12 hours after dosing) values for garenoxacin contained zero. No clinically relevant changes in the QTc or PR intervals were observed over a range of garenoxacin plasma concentrations (Cmax: 0.5-38.6 microg/mL, oral dose range; 3.36-21.4 microg/mL, intravenous dose range). No volunteer had a prolongation from baseline that exceeded established thresholds for the QTcB or QTcF interval (>450 milliseconds for men, >470 milliseconds for women) or the PR interval (>250 milliseconds). One subject had a change in QTcB of 67 milliseconds 4 hours after administration of garenoxacin 400 mg PO on day 7, but the actual value was 418 milliseconds (baseline, 351 milliseconds); the corresponding change in QTcF was 49 milliseconds (actual, 408 milliseconds; baseline, 359 milliseconds). The means for other derived ECG parameters were generally similar between garenoxacin-treated volunteers and placebo controls. In this retrospective analysis of data from healthy volunteers, garenoxacin had no clinically relevant dose-, route-of-administration-, or concentration-dependent effects on the QTc or PR interval across a dose range from 50 to 1200 mg/d.

Effects of a Pneumatic Tube System on Routine and Novel Hematology and Coagulation Parameters in Healthy Volunteers

Technologic advances affecting analyzers used in clinical laboratories have changed the methods used to obtain many laboratory measurements, and many novel parameters are now available. The effects of specimen transport through a pneumatic tube system on laboratory results obtained with such modern instruments are unclear. To determine the effects of sample transport through a pneumatic tube system on routine and novel hematology and coagulation parameters obtained on state-of-the-art analyzers. Paired blood samples from 33 healthy volunteers were either hand delivered to the clinical laboratory or transported through a pneumatic tube system. No statistically significant differences were observed for routine complete blood cell count and white cell differential parameters or markers of platelet activation, such as the mean platelet component, or of red cell fragmentation. When 2 donors who reported aspirin intake were excluded from the analysis, there was a statistically, but not clinically, significant impact of transport through the pneumatic tube system on the mean platelet component. There were no statistically significant differences for prothrombin time, activated partial thromboplastin time, waveform slopes for prothrombin time or activated partial thromboplastin time, fibrinogen, or fibrin monomers. Although further study regarding the mean platelet component may be required, transport through a pneumatic tube system has no clinically significant effect on hematology and coagulation results obtained with certain modern instruments in blood samples from healthy volunteers.