scholarly journals Pharmacokinetics in Serum and Leukocyte Exposures of Oral Azithromycin, 1,500 Milligrams, Given over a 3- or 5-Day Period in Healthy Subjects

1999 ◽  
Vol 43 (1) ◽  
pp. 163-165 ◽  
Author(s):  
Guy W. Amsden ◽  
Anne N. Nafziger ◽  
George Foulds
Keyword(s):  
Respiratory Tract ◽  
Healthy Volunteers ◽  
Healthy Subjects ◽  
Polymorphonuclear Leukocytes ◽  
Mononuclear Leukocytes ◽  
Drug Concentrations ◽  
Oral Azithromycin ◽  
Relevant Community

ABSTRACT The pharmacokinetics in serum and leukocyte (WBC) exposures of 1,500 mg of oral azithromycin administered as 3-day (500 mg/day, days 1 to 3) and 5-day (500 mg on day 1 and 250 mg/day on days 2 to 5) regimens were compared in 12 healthy volunteers. Serum, polymorphonuclear leukocytes, and mononuclear leukocytes were collected over a 12-day period from the start of each regimen. Results of the study indicate that the exposures of serum and both types of WBCs were similar with both regimens. Drug concentrations in day 12 WBCs were well above the MICs for all relevant community-acquired respiratory tract pathogens. Terminal half-lives in serum obtained by both regimens were essentially equal at 66 h and consistent with past reports. These results indicate that the standard 1,500-mg dose of oral azithromycin can be administered over either 5 or 3 days.

scholarly journals Intrapulmonary pharmacokinetics of azithromycin in healthy volunteers given five oral doses.

1996 ◽  
Vol 40 (11) ◽  
pp. 2582-2585 ◽  
Author(s):  
K M Olsen ◽  
G San Pedro ◽  
L P Gann ◽  
P O Gubbins ◽  
D M Halinski ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
High Performance ◽  
Blood Monocytes ◽  
Epithelial Lining Fluid ◽  
Once Daily ◽  
Drug Concentrations ◽  
Proven Efficacy ◽  
Study Support ◽  
Oral Doses ◽  
Oral Azithromycin

The intrapulmonary pharmacokinetics of oral azithromycin were studied in 25 healthy volunteers, each of whom received an initial dose of 500 mg and then 250 mg once daily for four additional doses. Bronchoscopy, bronchoalveolar lavage, and venipuncture were performed 4, 28, 76, 124, 172, 244, 340, and 508 h after the first dose was administered. Azithromycin concentrations in epithelial lining fluid (ELF), alveolar macrophages, peripheral blood monocytes, and serum were measured by high-performance liquid chromatography. Azithromycin was extensively concentrated in cells and ELF. Drug concentrations in AMs (peak mean +/- standard deviation, 464 +/- 65 micrograms/ml) exceeded 80 micrograms/ml up to 508 h (21 days) following the first dose, while concentrations in PBMs (peak, 124 +/- 28 micrograms/ml) exceeded 20 micrograms/ml up to 340 h (14 days). Azithromycin concentrations in ELF peaked at 124 h (3.12 +/- 0.93 micrograms/ml) and were detectable up to 172 h (7 days), when they were 20 times the concurrent serum concentrations. Although the clinical significance of antibiotic concentrations in these compartments is nuclear, the sustained lung tissue penetration and extensive phagocytic accumulation demonstrated in this study support the proven efficacy of azithromycin administered on a 5-day dosage schedule in the treatment of extracellular or intracellular pulmonary infections.

scholarly journals In Vivo Microdialysis Study of the Penetration of Daptomycin into Soft Tissues in Diabetic versus Healthy Volunteers

2008 ◽  
Vol 52 (11) ◽  
pp. 3941-3946 ◽  
Author(s):  
Aryun Kim ◽  
Larry A. Suecof ◽  
Christina A. Sutherland ◽  
Lihong Gao ◽  
Joseph L. Kuti ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Healthy Volunteers ◽  
Healthy Subjects ◽  
Soft Tissues ◽  
In Vivo Microdialysis ◽  
Free Drug ◽  
Target Tissue ◽  
Drug Concentrations ◽  
Complicated Skin

ABSTRACT Daptomycin is approved for the treatment of complicated skin and soft tissue infections, including diabetic wounds of the lower extremities, at a dose of 4 mg/kg of body weight once daily. For such localized tissue infections, drug concentrations in the interstitial space are an important determinant of successful therapy. In the diabetic population, peripheral arterial disease may limit antibiotic penetration into the target tissue. The objective of this study was to describe and compare the pharmacokinetic profiles of daptomycin in the interstitial fluid of soft tissues in diabetic and healthy volunteers by using in vivo microdialysis. Twelve subjects (six diabetic and six healthy) received a single 4-mg/kg dose of daptomycin intravenously. Samples of plasma and tissue were simultaneously collected over 24 h. Diabetic and healthy groups were matched in mean age (±10 years), gender ratio, mean weight (±10 kg), and creatinine clearance rate (±20 ml/min/1.73 m2). Pharmacokinetic parameters for plasma were similar between groups (P > 0.05). The mean peak drug concentrations ± standard deviations in tissue were 4.3 ± 3.3 μg/ml and 3.8 ± 1.4 μg/ml for diabetic and healthy subjects, respectively. The degree of tissue penetration, defined as the ratio of the area under the free drug concentration-time curve for tissue to that for plasma, was 0.93 ± 0.61 for diabetic subjects and 0.74 ± 0.09 for healthy subjects (P = 0.46). Daptomycin at 4 mg/kg penetrated well into the soft tissue, reaching concentrations approximately 70 to 90% of those of the free drug in plasma. Moreover, these free, bioactive concentrations in tissue exceeded the MICs for staphylococci and streptococci over the 24-h dosing interval.

Uptake of azithromycin by various cells and its intracellular activity under in vivo conditions.

1996 ◽  
Vol 40 (1) ◽  
pp. 75-79 ◽  
Author(s):  
A Wildfeuer ◽  
H Laufen ◽  
T Zimmermann
Keyword(s):  
Standard Deviation ◽  
Healthy Volunteers ◽  
Polymorphonuclear Leukocytes ◽  
Enrichment Factors ◽  
Phagocytic Cells ◽  
Once Daily ◽  
Intracellular Activity ◽  
Drug Concentrations ◽  
The Mean

The concentrations of azithromycin in polymorphonuclear leukocytes (PMNLs), monocytes, erythrocytes, and plasma were measured in six healthy volunteers after the last treatment of a 3-day regimen of 500 mg once daily. Marked enrichment of azithromycin was found in PMNLs and monocytes. The drug concentrations after the last dose amounted to 114 +/- 43 (mean +/- standard deviation) mg/liter at 12 h in PMNLs and 34 +/- 17 mg/liter at 6 h in monocytes. Fourteen days thereafter, azithromycin was still detectable in the PMNLs at 53 +/- 34 mg/liter and in the monocytes at 1 +/- 2 mg/liter, although the drug was no longer detectable in plasma (< 0.02 mg/liter). Maximum drug concentrations for azithromycin in plasma (0.40 +/- 0.30 mg/liter) and erythrocytes (0.15 +/- 0.05 mg/liter) at 3 h after the last administration were much lower and occurred earlier than those observed in the phagocytic cells. The mean enrichment factors (cellular/extracellular ratios) of azithromycin in phagocytes relative to plasma came to 231 +/- 150 and 3,924 +/- 584 at 3 and 120 h, respectively, for PMNLs and 83 +/- 55 and 523 +/- 285 at 3 and 120 h for monocytes, respectively, after the last dose. The phagocytosis tests with PMNLs separated from the blood of volunteers at various times after the last treatment confirmed the enhanced intracellular activity of these cells against staphylococci.

scholarly journals Effect of High-Density Lipoprotein from Healthy Subjects and Chronic Kidney Disease Patients on the CD14 Expression on Polymorphonuclear Leukocytes

2021 ◽  
Vol 22 (6) ◽  
pp. 2830
Author(s):  
Gerald Cohen
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
High Density Lipoprotein ◽  
Density Gradient ◽  
Healthy Subjects ◽  
Polymorphonuclear Leukocytes ◽  
Density Gradient Centrifugation ◽  
Gradient Centrifugation ◽  
Density Lipoprotein ◽  
Surface Expression

In uremic patients, high-density lipoprotein (HDL) loses its anti-inflammatory features and can even become pro-inflammatory due to an altered protein composition. In chronic kidney disease (CKD), impaired functions of polymorphonuclear leukocytes (PMNLs) contribute to inflammation and an increased risk of cardiovascular disease. This study investigated the effect of HDL from CKD and hemodialysis (HD) patients on the CD14 expression on PMNLs. HDL was isolated using a one-step density gradient centrifugation. Isolation of PMNLs was carried out by discontinuous Ficoll-Hypaque density gradient centrifugation. CD14 surface expression was quantified by flow cytometry. The activity of the small GTPase Rac1 was determined by means of an activation pull-down assay. HDL increased the CD14 surface expression on PMNLs. This effect was more pronounced for HDL isolated from uremic patients. The acute phase protein serum amyloid A (SAA) caused higher CD14 expression, while SAA as part of an HDL particle did not. Lipid raft disruption with methyl-β-cyclodextrin led to a reduced CD14 expression in the absence and presence of HDL. HDL from healthy subjects but not from HD patients decreased the activity of Rac1. Considering the known anti-inflammatory effects of HDL, the finding that even HDL from healthy subjects increased the CD14 expression was unexpected. The pathophysiological relevance of this result needs further investigation.

scholarly journals The use of a neck brace does not influence visual vertical perception

2011 ◽  
Vol 69 (3) ◽  
pp. 509-512 ◽  
Author(s):  
Martha Funabashi ◽  
Natya N.L. Silva ◽  
Luciana M. Watanabe ◽  
Taiza E.G Santos-Pontelli ◽  
José Fernando Colafêmina ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Healthy Subjects ◽  
Afferent Input ◽  
Subjective Visual Vertical ◽  
Sensory Receptors ◽  
Ocular Torsion ◽  
Vertical Orientation ◽  
Mean Values ◽  
Visual Vertical ◽  
The Mean

Subjective visual vertical (SVV) evaluates the individual's capacity to determine the vertical orientation. Using a neck brace (NB) allow volunteers' heads fixation to reduce cephalic tilt during the exam, preventing compensatory ocular torsion and erroneous influence on SVV result. OBJECTIVE: To analyze the influence of somatosensory inputs caused by a NB on the SVV. METHOD: Thirty healthy volunteers performed static and dynamic SVV: six measures with and six without the NB. RESULTS: The mean values for static SVV were -0.075º±1.15º without NB and -0.372º±1.21º with NB. For dynamic SVV in clockwise direction were 1.73º±2.31º without NB and 1.53º±1.80º with NB. For dynamic SVV in counterclockwise direction was -1.50º±2.44º without NB and -1.11º±2.46º with NB. Differences between measurements with and without the NB were not statistically significant. CONCLUSION: Although the neck has many sensory receptors, the use of a NB does not provide sufficient afferent input to change healthy subjects' perception of visual verticality.

Increased frequency of aberrant CSF circulation in schizophrenic patients compared to healthy volunteers

1996 ◽  
Vol 11 (1) ◽  
pp. 16-20 ◽  
Author(s):  
G Oxenstierna ◽  
G Bergstrand ◽  
G Edman ◽  
L Flyckt ◽  
H Nybäck ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Healthy Subjects ◽  
Flow Dynamics ◽  
Resonance Imaging ◽  
Improved Method ◽  
Csf Circulation ◽  
Recent Developments ◽  
Schizophrenic Patients ◽  
Duration Of Disease ◽  
Csf Levels

SummaryIn a previous cisternographic study of the cerebrospinal fluid (CSF) circulation in schizophrenic patients, indications for disturbed flow dynamics were found in 10 of 30 subjects. In order to replicate and investigate the clinical and pathophysiological significance of this finding, 39 schizophrenic patients and 42 healthy subjects were examined with an improved method for measurement of CSF circulation. 99mTc-DTPA was injected intrathecally and the gamma cisternograms were evaluated blindly. Correlations between cisternography findings and age, duration of disease, previous hospitalizations, positive or negative symptomatology, exposure to neuroleptics, psychiatric family history, CT findings and CSF levels of protein, tryptophan and monoamine metabolites, were calculated. Seven of the patients showed abnormalities in the cisternograms with a slow or obstructed flow of CSF over the convexities (P < 0.01) whereas none of the healthy volunteers showed abnormalities. There were no correlations between disturbed CSF circulation in the patients and the clinical and biochemical parameters, thus the significance of the deviations, similar to other biological aberrations found in schizophrenic patients, is not known. Recent developments in magnetic resonance imaging offer new possibilities to further examine CSF circulation abnormalities in schizophrenia.

scholarly journals Safety, pharmacokinetics, and reversal of apixaban anticoagulation with andexanet alfa

2017 ◽  
Vol 1 (21) ◽  
pp. 1827-1838 ◽  
Author(s):  
Deborah Siegal ◽  
Genmin Lu ◽  
Janet M. Leeds ◽  
Mark Karbarz ◽  
Janice Castillo ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Healthy Subjects ◽  
Preclinical Models ◽  
Key Points ◽  
Andexanet Alfa

Key Points Andexanet reversed apixaban anticoagulation in healthy volunteers within minutes after administration and for the duration of infusion. Andexanet was generally well tolerated, with no evidence of prothrombotic activity in preclinical models and in healthy subjects.

scholarly journals Multi-Atlas MRI-Based Striatum Segmentation for 123I-FP-CIT SPECT (DAT-SPECT) Compared With the Bolt Method and SPECT-Atlas-Based Segmentation Method Toward the Accurate Diagnosis of Parkinson's Disease/Syndrome

2021 ◽  
Vol 8 ◽  
Author(s):  
Koji Sohara ◽  
Tetsuro Sekine ◽  
Amane Tateno ◽  
Sunao Mizumura ◽  
Masaya Suda ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Healthy Subjects ◽  
Occipital Lobe ◽  
Occipital Cortex ◽  
Accurate Diagnosis ◽  
Reference Region ◽  
Uptake Ratio ◽  
Segmentation Method ◽  
Clinical Methods ◽  
Dat Spect

Aims: This study aimed to analyze the performance of multi-atlas MRI-based parcellation for 123I-FP-CIT SPECT (DAT-SPECT) in healthy volunteers. The proposed method was compared with the SPECT-atlas-based and Bolt methods. 18F-FE-PE2I-PET (DAT-PET) was used as a reference.Methods: Thirty healthy subjects underwent DAT-SPECT, DAT-PET, and 3D-T1WI-MRI. We calculated the striatum uptake ratio (SUR/SBR), caudate uptake ratio (CUR), and putamen uptake ratio (PUR) for DAT-SPECT using the multi-atlas MRI-based method, SPECT-atlas-based method, and Bolt method. In the multi-atlas MRI-based method, the cerebellum, occipital cortex, and whole-brain were used as reference regions. The correlation of age with DAT-SPECT activity and the correlations of SUR/SBR, CUR, and PUR between DAT-SPECT and DAT-PET were calculated by each of the three methods.Results: The correlation between age and SUR/SBR for DAT-SPECT based on the multi-atlas MRI-based method was comparable to that based on the SPECT-atlas-based method (r = −0.441 to −0.496 vs. −0.488). The highest correlation between DAT-SPECT and DAT-PET was observed using the multi-atlas MRI-based method with the occipital lobe defined as the reference region compared with the SPECT-atlas-based and Bolt methods (SUR, CUR, and PUR: 0.687, 0.723, and 0.676 vs. 0.698, 0.660, and 0.616 vs. 0.655).Conclusion: Multi-atlas MRI-based parcellation with the occipital lobe defined as the reference region was at least comparable to the clinical methods.

scholarly journals Exhaled Breath Condensate: Pilot Study of the Method and Initial Experience in Healthy Subjects

2018 ◽  
Vol 61 (1) ◽  
pp. 8-16
Author(s):  
Eva Peterová ◽  
Jaroslav Chládek ◽  
Darina Kohoutová ◽  
Veronika Knoblochová ◽  
Paula Morávková ◽  
...  
Keyword(s):  
Pilot Study ◽  
Healthy Volunteers ◽  
Coefficient Of Variation ◽  
Healthy Subjects ◽  
Lung Diseases ◽  
Exhaled Breath Condensate ◽  
Exhaled Breath ◽  
Initial Experience ◽  
Major Disadvantage ◽  
Breath Condensate

Analysis of Exhaled breath condensate (EBC) is a re-discovered approach to monitoring the course of the disease and reduce invasive methods of patient investigation. However, the major disadvantage and shortcoming of the EBC is lack of reliable and reproducible standardization of the method. Despite many articles published on EBC, until now there is no clear consensus on whether the analysis of EBC can provide a clue to diagnosis of the diseases. The purpose of this paper is to investigate our own method, to search for possible standardization and to obtain our own initial experience. Thirty healthy volunteers provided the EBC, in which we monitored the density, pH, protein, chloride and urea concentration. Our results show that EBC pH is influenced by smoking, and urea concentrations are affected by the gender of subjects. Age of subjects does not play a role. The smallest coefficient of variation between individual volunteers is for density determination. Current limitations of EBC measurements are the low concentration of many biomarkers. Standardization needs to be specific for each individual biomarker, with focusing on optimal condensate collection. EBC analysis has a potential become diagnostic test, not only for lung diseases.

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