Comparison of bronchopulmonary pharmacokinetics of clarithromycin and azithromycin.

1996 ◽  
Vol 40 (10) ◽  
pp. 2375-2379 ◽  
Author(s):  
K B Patel ◽  
D Xuan ◽  
P R Tessier ◽  
J H Russomanno ◽  
R Quintiliani ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
High Performance ◽  
Tissue Concentration ◽  
Epithelial Lining ◽  
Assay Sensitivity ◽  
Epithelial Lining Fluid ◽  
Once Daily ◽  
Time Points ◽  
Plasma Pharmacokinetics ◽  
Absolute Concentrations

The bronchopulmonary and plasma pharmacokinetics of clarithromycin (CLA; 500 mg given twice daily for nine doses) or azithromycin (AZ; 500 mg for the first dose and then 250 mg once daily for four doses) were assessed in 41 healthy nonsmokers. Bronchoalveolar lavage was performed at 4, 8, 12, or 24 h after administration of the last dose. The concentrations (mean +/- standard deviation) of CLA, 14-hydroxyclarithromycin, and AZ were measured in plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) cells by high-performance liquid chromatography assay. The concentrations of CLA achieved in ELF were 34.02 +/- 5.16 micrograms/ml at 4 h, 20.63 +/- 4.49 micrograms/ml at 8 h, 23.01 +/- 11.9 micrograms/ml at 12 h, and 4.17 +/- 0.29 microgram/ml at 24 h, whereas at the same time points AZ concentrations remained below the limit of assay sensitivity (0.01 microgram/ml) for all but two subjects. The concentrations of CLA in the AM cells were significantly higher than those of AZ at 8 h (703 +/- 235 and 388 +/- 53 micrograms/ml, respectively). However, the ratio of the concentration in AM cells/concentration in plasma was significantly higher for AZ than for CLA for all time points because of the lower concentration of AZ in plasma. These results indicate that while AZ has higher tissue concentration to plasma ratios, as shown by other investigators, the absolute concentrations of CLA in AM cells and ELF are higher for up to 8 and 12 h, respectively, after administration of the last dose.

scholarly journals Comparison of Plasma, Epithelial Lining Fluid, and Alveolar Macrophage Concentrations of Solithromycin (CEM-101) in Healthy Adult Subjects

2012 ◽  
Vol 56 (10) ◽  
pp. 5076-5081 ◽  
Author(s):  
Keith A. Rodvold ◽  
Mark H. Gotfried ◽  
J. Gordon Still ◽  
Kay Clark ◽  
Prabhavathi Fernandes
Keyword(s):  
Steady State ◽  
High Performance ◽  
Healthy Adult ◽  
Plasma Concentrations ◽  
Epithelial Lining ◽  
Time Curve ◽  
Epithelial Lining Fluid ◽  
Once Daily ◽  
Drug Concentrations ◽  
The Mean

ABSTRACTThe steady-state concentrations of solithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained from intrapulmonary samples during bronchoscopy and bronchoalveolar lavage (BAL) in 30 healthy adult subjects. Subjects received oral solithromycin at 400 mg once daily for five consecutive days. Bronchoscopy and BAL were carried out once in each subject at either 3, 6, 9, 12, or 24 h after the last administered dose of solithromycin. Drug concentrations in plasma, ELF, and AM were assayed by a high-performance liquid chromatography-tandem mass spectrometry method. Solithromycin was concentrated extensively in ELF (range of mean [± standard deviation] concentrations, 1.02 ± 0.83 to 7.58 ± 6.69 mg/liter) and AM (25.9 ± 20.3 to 101.7 ± 52.6 mg/liter) in comparison with simultaneous plasma concentrations (0.086 ± 0.070 to 0.730 ± 0.692 mg/liter). The values for the area under the concentration-time curve from 0 to 24 h (AUC0–24values) based on mean and median ELF concentrations were 80.3 and 63.2 mg · h/liter, respectively. The ratio of ELF to plasma concentrations based on the mean and median AUC0–24values were 10.3 and 10.0, respectively. The AUC0–24values based on mean and median concentrations in AM were 1,498 and 1,282 mg · h/L, respectively. The ratio of AM to plasma concentrations based on the mean and median AUC0–24values were 193 and 202, respectively. Once-daily oral dosing of solithromycin at 400 mg produced steady-state concentrations that were significantly (P< 0.05) higher in ELF (2.4 to 28.6 times) and AM (44 to 515 times) than simultaneous plasma concentrations throughout the 24-h period after 5 days of solithromycin administration.

scholarly journals Rifampin Reduces Concentrations of Trimethoprim and Sulfamethoxazole in Serum in Human Immunodeficiency Virus-Infected Patients

2001 ◽  
Vol 45 (11) ◽  
pp. 3238-3241 ◽  
Author(s):  
Esteban Ribera ◽  
Leonor Pou ◽  
Antoni Fernandez-Sola ◽  
Francisco Campos ◽  
Rosa M. Lopez ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
High Performance Liquid Chromatography ◽  
High Performance ◽  
Parent Drug ◽  
Time Curve ◽  
Once Daily ◽  
Concentration Time ◽  
Antituberculosis Treatment ◽  
Immunodeficiency Virus ◽  
Before And After

ABSTRACT To determine whether rifampin reduces concentrations of trimethoprim (TMP) and sulfamethoxazole (SMX) in serum of human immunodeficiency virus (HIV)-infected persons, levels of these agents were determined by high-performance liquid chromatography before and after more than 12 days of standard antituberculosis treatment for 10 patients who had been taking one double-strength tablet of co-trimoxazole once daily for more than 1 month. Statistically significant, 47 and 23% decreases in TMP and SMX mean areas under the concentration-time curve from 0 to 24 h (AUC0–24), respectively, were observed after administration of rifampin.N-Acetyl-SMX profiles without and with rifampin were similar. The steady-state AUC0–24 metabolite/parent drug ratio increased by 32% with rifampin administration. Our study shows that rifampin reduces profiles of TMP and SMX in serum of HIV-infected patients.

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 Intact glycosphingolipidomic analysis of the cell membrane during differentiation yields extensive glycan and lipid changes

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Maurice Wong ◽  
Gege Xu ◽  
Dayoung Park ◽  
Mariana Barboza ◽  
Carlito B. Lebrilla
Keyword(s):  
Mass Spectrometry ◽  
High Performance Liquid Chromatography ◽  
High Performance ◽  
Animal Tissue ◽  
Cell Recognition ◽  
Dynamic Variation ◽  
Time Points ◽  
Flight Mass Spectrometry ◽  
A Cell ◽  
Tof Ms

AbstractGlycosphingolipids (GSLs) are found in cellular membranes of most organisms and play important roles in cell-cell recognition, signaling, growth, and adhesion, among others. A method based on nanoflow high performance liquid chromatography-chip-quadrupole-time-of-flight mass spectrometry (nanoHPLC Chip-Q-TOF MS) was applied towards identifying and quantifying intact GSLs from a variety of samples, including cultured cell lines and animal tissue. The method provides the composition and sequence of the glycan, as well as variations in the ceramide portion of the GSL. It was used to profile the changes in the glycolipidome of Caco-2 cells as they undergo differentiation. A total of 226 unique GSLs were found among Caco-2 samples from five differentiation time-points. The method provided a comprehensive glycolipidomic profile of a cell during differentiation to yield the dynamic variation of intact GSL structures.

scholarly journals Is One Sample Enough? β-Lactam Target Attainment and Penetration into Epithelial Lining Fluid Based on Multiple Bronchoalveolar Lavage Sampling Time Points in a Swine Pneumonia Model

2018 ◽  
Vol 63 (2) ◽  
pp. e01922-18 ◽  
Author(s):  
Ana Motos ◽  
Joseph L. Kuti ◽  
Gianluigi Li Bassi ◽  
Antoni Torres ◽  
David P. Nicolau
Keyword(s):  
Antimicrobial Agents ◽  
Free Drug ◽  
Sampling Time ◽  
Epithelial Lining ◽  
Target Attainment ◽  
Epithelial Lining Fluid ◽  
Time Points ◽  
Optimal Dosing ◽  
Exposure Target ◽  
Investigational Agents

ABSTRACTDescribing the disposition of antimicrobial agents at the site of infection is crucial to guide optimal dosing for investigational agents. For antibiotics in development for the treatment of nosocomial pneumonia, concentrations in the epithelial lining fluid (ELF) of the lung are frequently determined from a bronchoscopy at a single time point. The influence of profiles constructed from a single ELF concentration point for each subject has never been reported. This study compares the pharmacokinetics of two β-lactams, ceftolozane and piperacillin, among different ELF sampling approaches using simulated human regimens in a swine pneumonia model. Plasma and ELF concentration-time profiles were characterized in two-compartment models by the use of robustly sampled ELF concentrations and by the random selection of one or two ELF concentrations from each swine. A 5,000-subject Monte Carlo simulation was performed for each model to define the ELF penetration, as described by the ratio of the area under the concentration curve (AUC) for ELF to the AUC for free drug in plasma (AUCELF/fAUCplasma) and the probability of target attainment (PTA). Given the intersubject variability of the ELF penetrations observed, differences between the models developed using robust numbers of ELF samples versus one or two ELF samples per swine were minimal for both drugs (maximum dispersion < 20%). Using a threshold exposure target of 60% of the time that the free drug concentration remains above the MIC target, the ceftolozane and piperacillin regimens achieved PTAs of ≥90% at MICs of up to 4 and 1 μg/ml, respectively, among the different ELF sampling strategies. These models suggest that the ELF models constructed with concentrations from sparse ELF sampling time points result in exposure estimates similar to those constructed from robustly sampled ELF profiles.

Short-Dwell Cycling Intraperitoneal Cefazolin plus Ceftazidime in Peritoneal Dialysis Patients

2017 ◽  
Vol 37 (2) ◽  
pp. 218-224 ◽  
Author(s):  
Sadudee Peerapornratana ◽  
Pajaree Chariyavilaskul ◽  
Talerngsak Kanjanabuch ◽  
Kearkiat Praditpornsilpa ◽  
Somchai Eiam-Ong ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Peritoneal Dialysis ◽  
High Performance ◽  
Inhibitory Concentration ◽  
Volume Overload ◽  
Plasma Samples ◽  
Dialysis Patients ◽  
Time Points ◽  
Current Guidelines

BackgroundCurrent guidelines suggest that intraperitoneal (IP) antibiotics should be administered only in a long peritoneal dialysis (PD) dwell (≥ 6 hours). The long dwell might result in low ultrafiltration and volume overload. We aim to examine plasma and dialysate concentration of cefazolin and ceftazidime after IP administration in a short-dwell (≤ 2 hours) automated cycling exchange.MethodsStable PD patients without peritonitis were invited to participate in the present study. Patients underwent 5 2-liter exchanges of PD fluid over 10 hours by the PD cycling machine without last fill or additional dwell. Cefazolin and ceftazidime (20 mg/kg each) were added to the first 5-liter bag of 2.5% dextrose PD fluid that was placed on the warmer of the PD cycling machine. Plasma samples were collected at 12 time-points over 24 hours. Dialysate samples from each exchange were also collected. Antibiotic concentrations in plasma and dialysate were then determined by high-performance liquid chromatography (HPLC).ResultsSix stable PD patients without peritonitis participated in the study. Dialysate cefazolin and ceftazidime were consistently high throughout the PD session in all patients (26 - 360 mg/L). Plasma cefazolin and ceftazidime exceeded the minimal inhibitory concentration (MIC) for susceptible organisms (≤ 8 mg/L) within 2 hours (cefazolin 28.5 ± 8.0 and ceftazidime 12.5 ± 3.4 mg/L), peak at 10 hours (51.1 ± 14.1 and 23.0 ± 5.2 mg/L) and sustained well above the MIC at 24 hours (42.0 ± 9.6 and 17.1 ± 3.1 mg/L).ConclusionsThe short-dwell cycling IP cefazolin and ceftazidime could provide adequate plasma concentration for up to 24 hours. Daily short-dwell cycling IP cefazolin and ceftazidime might be used to treat peritonitis in PD patients already using a PD cycling machine as well as selected continuous ambulatory PD (CAPD) patients who need shorter dwells during peritonitis due to increasing peritoneal solute transport.

scholarly journals Propofol infusions using a human target controlled infusion (TCI) pump in chimpanzees (Pan troglodytes)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
T. Miyabe-Nishiwaki ◽  
A. Kaneko ◽  
A. Yamanaka ◽  
N. Maeda ◽  
J. Suzuki ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Pan Troglodytes ◽  
High Performance ◽  
Pharmacokinetic Models ◽  
Blood Samples ◽  
Time Points ◽  
Acceptable Range ◽  
Target Controlled Infusion ◽  
Human Pharmacokinetic

AbstractChimpanzees are genetically and physiologically similar to humans. Several pharmacokinetic models of propofol are available and target controlled infusion (TCI) of propofol is established in humans, but not in chimpanzees. The purpose of this study was to investigate if human pharmacokinetic models can accurately predict propofol plasma concentration (Cp) in chimpanzees and if it is feasible to perform TCI in chimpanzees. Ten chimpanzees were anaesthetized for regular veterinary examinations. Propofol was used as an induction or maintenance agent. Blood samples were collected from a catheter in a cephalic vein at 3–7 time points between 1 and 100 min following the propofol bolus and/or infusion in five chimpanzees, or TCI in six chimpanzees. Cp was measured using high-performance liquid chromatography. The Marsh, Schnider and Eleveld human pharmacokinetic models were used to predict Cp for each case and we examined the predictive performances of these models using the Varvel criteria Median PE and Median APE. Median PE and Median APE for Marsh, Schnider and Eleveld models were within or close to the acceptable range. A human TCI pump was successfully maintained propofol Cp during general anesthesia in six chimpanzees. Human propofol pharmacokinetic models and TCI pumps can be applied in chimpanzees.

scholarly journals Changes in the content of water-soluble vitamins in Actinidia chinensis during cold storage

2016 ◽  
Vol 81 (6) ◽  
pp. 623-632
Author(s):  
Xian-Bo Zhu ◽  
Liang Pan ◽  
WU. Wei ◽  
Jia-Qing Pen ◽  
Yin-Wei Qi ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Cold Storage ◽  
High Performance ◽  
Water Soluble ◽  
Actinidia Chinensis ◽  
Time Points ◽  
Wild Fruit ◽  
And Control ◽  
Time Point

We assessed the effects of cold storage on nine water-soluble vitamins in 7 cultivars of Actinidia chinensis (kiwifruit) using high-performance liquid chromatography. Samples were collected at three time points during cold storage: one day, 30 days, and when edible. We found that vitamin C in most cultivars was raised with cold storage, but there was no consistent increased or decreased trend for other water-soluble vitamins across cultivars in storage. After one day of cold storage, vitamins B1 and B2 were the most prevalent vitamins in Control (wild) fruit, while vitamins B5 and B6 were most prevalent in the Hongyang and Qihong cultivars. However, B12 was the most prevalent vitamin in the Qihong cultivar after 30 days of cold storage. Vitamins B3, B7, B9, and C were detected at the edible time point in Huayou, Hongyang, Jinnong-2, and Control fruit. Vitamin contents varied significantly among cultivars of kiwifruit following different durations of cold storage. Out of the three durations tested, a period of 30 days in cold storage was the most suitable for the absorption of water-soluble vitamins by A. chinensis.

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