scholarly journals Pharmacokinetics of Colistin in Cerebrospinal Fluid after Intraventricular Administration of Colistin Methanesulfonate

2012 ◽  
Vol 56 (8) ◽  
pp. 4416-4421 ◽  
Author(s):  
Roberto Imberti ◽  
Maria Cusato ◽  
Giovanni Accetta ◽  
Valeria Marinò ◽  
Francesco Procaccio ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
High Performance ◽  
Compartment Model ◽  
Intraventricular Administration ◽  
Central Nervous System Infections ◽  
Daily Dose ◽  
Csf Pharmacokinetics ◽  
Colistin Methanesulfonate ◽  
The One ◽  
Microbiological Cure

ABSTRACTIntraventricular colistin, administered as colistin methanesulfonate (CMS), is the last resource for the treatment of central nervous system infections caused by panresistant Gram-negative bacteria. The doses and daily regimens vary considerably and are empirically chosen; the cerebrospinal fluid (CSF) pharmacokinetics of colistin after intraventricular administration of CMS has never been characterized. Nine patients (aged 18 to 73 years) were treated with intraventricular CMS (daily doses of 2.61 to 10.44 mg). Colistin concentrations were measured using a selective high-performance liquid chromatography (HPLC) assay. The population pharmacokinetics analysis was performed with the P-Pharm program. The pharmacokinetics of colistin could be best described by the one-compartment model. The estimated values (means ± standard deviations) of apparent CSF total clearance (CL/Fm, where Fm is the unknown fraction of CMS converted to colistin) and terminal half-life (t1/2λ) were 0.033 ± 0.014 liter/h and 7.8 ± 3.2 h, respectively, and the average time to the peak concentration was 3.7 ± 0.9 h. A positive correlation between CL/Fm and the amount of CSF drained (range 40 to 300 ml) was observed. When CMS was administered at doses of ≥5.22 mg/day, measured CSF concentrations of colistin were continuously above the MIC of 2 μg/ml, and measured values of trough concentration (Ctrough) ranged between 2.0 and 9.7 μg/ml. Microbiological cure was observed in 8/9 patients. Intraventricular administration of CMS at doses of ≥5.22 mg per day was appropriate in our patients, but since external CSF efflux is variable and can influence the clearance of colistin and its concentrations in CSF, the daily dose of 10 mg suggested by the Infectious Diseases Society of America may be more prudent.

scholarly journals Cerebrospinal fluid ceftazidime kinetics in patients with external ventriculostomies.

1996 ◽  
Vol 40 (3) ◽  
pp. 763-766 ◽  
Author(s):  
R Nau ◽  
H W Prange ◽  
M Kinzig ◽  
A Frank ◽  
A Dressel ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
High Performance ◽  
Elimination Half ◽  
Daily Dose ◽  
Order Of Magnitude ◽  
The Central Nervous System ◽  
Occlusive Hydrocephalus ◽  
A Minor

Ceftazidime has proven to be effective for the treatment of bacterial meningitis caused by multiresistant gram-negative bacteria. Since nosocomial central nervous system infections are often accompanied by only a minor dysfunction of the blood-cerebrospinal fluid (CSF) barrier, patients with noninflammatory occlusive hydrocephalus who had undergone external ventriculostomy were studied (n = 8). Serum and CSF were drawn repeatedly after the administration of the first dose of ceftazidime (3 g over 30 min intravenously), and concentrations were determined by high-performance liquid chromatography by using UV detection. The concentrations of ceftazidime in CSF were maximal at 1 to 13 h (median, 5.5 h) after the end of the infusion and ranged from 0.73 to 2.80 mg/liter (median, 1.56 mg/liter). The elimination half-lives were 3.13 to 18.1 h (median, 10.7 h) in CSF compared with 2.02 to 5.24 h (median, 3.74 h) in serum. The ratios of the areas under the concentration-time curves in CSF and serum (AUCCSF/AUCS) ranged from 0.027 to 0.123 (median, 0.054). After the administration of a single dose of 3 g, the maximum concentrations of ceftazidime in CSF were approximately four times higher than those after the administration of 2-g intravenous doses of cefotaxime (median, 0.44 mg/liter) and ceftriaxone (median, 0.43 mg/liter) (R. Nau, H. W. Prange, P. Muth, G. Mahr, S. Menck, H. Kolenda, and F. Sörgel, Antimicrob. Agents Chemother. 37:1518-1524, 1993). The median AUCCSF/AUCS ratio of ceftazidime was slightly below that of cefotaxime (0.12), but it was 1 order of magnitude above the median AUCCSF/AUCS of ceftriaxone (0.007) (Nau et al., Antimicrob. Agents Chemother. 37:1518-1524, 1993). The concentrations of ceftazidime observed in CSF were above the MICs for most Pseudomonas aeruginosa strains. However, they are probably not high enough to be rapidly bactericidal. For this reason, the daily dose should be increased to 12 g in cases of P. aeruginosa infections of the central nervous system when the blood-CSF barrier is minimally impaired.

Effective ribavirin concentration in hamster brains for antiviral chemotherapy for subacute sclerosing panencephalitis.

1996 ◽  
Vol 40 (1) ◽  
pp. 241-243 ◽  
Author(s):  
T Ishii ◽  
M Hosoya ◽  
S Mori ◽  
S Shigeta ◽  
H Suzuki
Keyword(s):  
Cerebrospinal Fluid ◽  
High Performance ◽  
Subacute Sclerosing Panencephalitis ◽  
Effective Concentration ◽  
Intraventricular Administration ◽  
Sspe Virus ◽  
Antiviral Chemotherapy ◽  
Potential Use

The ribavirin concentration in hamster brains was measured by a high-performance liquid chromatography (HPLC) system and a bioassay system. When ribavirin was administered intracranially at a dosage of 10 mg/kg of body weight per day for 10 days, a dosage which results in 100% survival of hamsters infected with subacute sclerosing panencephalitis (SSPE) virus and which inhibits the replication of SSPE virus in hamster brains, the ribavirin concentration in the brains estimated by HPLC and bioassay was kept higher than 50 micrograms/g for 10 days. The effective concentration in vivo corresponds to the concentration at which ribavirin completely inhibits the replication of SSPE virus in vitro. The maximal tolerable ribavirin concentration for hamsters was calculated to be 150 micrograms/g. Although ribavirin shows toxicity to the animals at a relatively low concentration (250 to 400 micrograms/g), intrathecal or intraventricular administration of ribavirin should be explored for potential use in the treatment of patients with SSPE, while the ribavirin concentration in cerebrospinal fluid or brain tissue should be monitored.

scholarly journals Combined Intravenous and Intraventricular Administration of Colistin Methanesulfonate in Critically Ill Patients with Central Nervous System Infection

2013 ◽  
Vol 57 (4) ◽  
pp. 1938-1940 ◽  
Author(s):  
Mairi Ziaka ◽  
Sophia L. Markantonis ◽  
Marizoza Fousteri ◽  
Paris Zygoulis ◽  
Dimitris Panidis ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Critically Ill ◽  
Intravenous Administration ◽  
Critically Ill Patients ◽  
External Ventricular Drain ◽  
Central Nervous System Infection ◽  
Intraventricular Administration ◽  
Colistin Methanesulfonate

ABSTRACTColistin pharmacokinetics were prospectively studied after intravenous administration of colistin methanesulphonate in critically ill patients without central nervous system infection (controls,n= 5) and in patients with external ventricular drain-associated ventriculitis after intravenous administration (EVDViv,n= 3) or combined intravenous/intraventricular administration (EVDVcomb,n= 4). Cerebrospinal fluid (CSF)/serum colistin concentration ratios were higher in EVDViv than in control patients (11% versus 7%,P≤ 0.05) and in EVDVcomb compared to all other patients (P< 0.0001). CSF colistin concentrations above the MIC of 0.5 μg/ml were achieved only in EVDVcomb patients.

Extended CSF cytarabine exposure following intrathecal administration of DTC 101.

1993 ◽  
Vol 11 (11) ◽  
pp. 2186-2193 ◽  
Author(s):  
S Kim ◽  
E Chatelut ◽  
J C Kim ◽  
S B Howell ◽  
C Cates ◽  
...  
Keyword(s):  
Lateral Ventricle ◽  
High Performance ◽  
Maximum Tolerated Dose ◽  
Intrathecal Administration ◽  
Neoplastic Meningitis ◽  
Intraventricular Injection ◽  
Intraventricular Administration ◽  
Csf Pharmacokinetics ◽  
La Jolla ◽  
The Right

PURPOSE The aims of the present study were to determine ventricular and lumbar CSF pharmacokinetics and the maximum-tolerated dose (MTD) of DTC 101 (DepoFoam; DepoTech Corp, La Jolla, CA) following intraventricular administration. PATIENTS AND METHODS Twelve patients with neoplastic meningitis were treated with escalating doses of DTC 101. CSF samples were obtained from the right lateral ventricle or from the lumbar subarachnoid space and cytarabine concentrations were determined by high-performance liquid chromatography. RESULTS Therapeutic ventricular CSF concentrations were maintained for 9 +/- 2 days following administration of a single dose of DTC 101 into the lateral ventricle. Lumbar cytarabine concentrations became equal to those in the ventricle within the first 6 hours after intraventricular injection, and the subsequent decay in concentrations of free and total cytarabine were the same at both sites. Following intralumbar administration, the peak ventricular concentration of free cytarabine was reached within 1 day, and therapeutic ventricular CSF levels were maintained for several days. Therapeutic intralumbar concentration of free cytarabine was maintained for up to 14 days. The MTD was 75 mg of DTC 101, and seven of nine patients manifested cytologic responses. CONCLUSION Extended CSF exposure to therapeutic cytarabine concentrations was achieved after a single intraventricular or intralumbar dose of DTC 101, permitting drug administration once every 2 weeks.

scholarly journals Intranasal administration of the chemotherapeutic perillyl alcohol results in selective delivery to the cerebrospinal fluid in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Geetika Nehra ◽  
Shannon Andrews ◽  
Joan Rettig ◽  
Michael N. Gould ◽  
Jill D. Haag ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Tumors ◽  
Nasal Mucosa ◽  
Brain Cancer ◽  
Intranasal Administration ◽  
High Performance ◽  
Early Stage ◽  
Plasma Concentrations ◽  
Perillyl Alcohol ◽  
Systemic Absorption

AbstractPerillyl alcohol (POH) has been extensively studied for the treatment of peripheral and primary brain tumors. The intranasal route of administration has been preferred for dosing POH in early-stage clinical trials associated with promising outcomes in primary brain cancer. However, it is unclear how intranasal POH targets brain tumors in these patients. Multiple studies indicate that intranasally applied large molecules may enter the brain and cerebrospinal fluid (CSF) through direct olfactory and trigeminal nerve-associated pathways originating in the nasal mucosa that bypass the blood–brain barrier. It is unknown whether POH, a small molecule subject to extensive nasal metabolism and systemic absorption, may also undergo direct transport to brain or CSF from the nasal mucosa. Here, we compared CSF and plasma concentrations of POH and its metabolite, perillic acid (PA), following intranasal or intravascular POH application. Samples were collected over 70 min and assayed by high-performance liquid chromatography. Intranasal administration resulted in tenfold higher CSF-to-plasma ratios for POH and tenfold higher CSF levels for PA compared to equal dose intravascular administration. Our preclinical results demonstrate POH undergoes direct transport from the nasal mucosa to the CSF, a finding with potential significance for its efficacy as an intranasal chemotherapeutic for brain cancer.

scholarly journals Comparative Study of the Field Performances of Pressure-Grouted Micropiles Using Gravity and Packers

2021 ◽  
Vol 11 (15) ◽  
pp. 6736
Author(s):  
Ong Heo ◽  
Yeowon Yoon ◽  
Jinung Do
Keyword(s):  
Urban Areas ◽  
High Performance ◽  
Driving Forces ◽  
Field Performance ◽  
Underground Space ◽  
Creep Tests ◽  
Deep Foundation ◽  
Installation Depth ◽  
Pressure Grouting ◽  
The One

When underground space requires excavation in areas below the water table, the foundation system suffers from buoyancy, which leads to the uplifting of the superstructure. A deep foundation system can be used; however, in cases where a hard layer is encountered, high driving forces and corresponding noises cause civil complaints in urban areas. Micropiles can be an effective alternative option, due to their high performance despite a short installation depth. Pressurized grouting is used with a packer to induce higher interfacial properties between micropile and soil. In this study, the field performance of micropiles installed using gravitational grouting or pressure-grouted using either a geotextile packer or rubber packer was comparatively evaluated by tension and creep tests. Micropiles were installed using pressure grouting in weak and fractured zones. As results, the pressure-grouted micropiles showed more stable and stronger behaviors than ones installed using the gravitational grouting. Moreover, the pressure-grouted micropile installed using the rubber packer showed better performance than the one using the geotextile packer.

scholarly journals AFX Zeolite for Use as a Support of NH3-SCR Catalyst Mining through AICE Joint Research Project of Industries–Academia–Academia

Catalysts ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 163
Author(s):  
Masaru Ogura ◽  
Yumiko Shimada ◽  
Takeshi Ohnishi ◽  
Naoto Nakazawa ◽  
Yoshihiro Kubota ◽  
...  
Keyword(s):  
High Performance ◽  
Ionic Species ◽  
Research Project ◽  
Joint Research ◽  
Structure Directing Agent ◽  
Scr Catalyst ◽  
Organic Structure ◽  
Nh3 Scr ◽  
Joint Research Project ◽  
The One

This paper introduces a joint industries–academia–academia research project started by researchers in several automobile companies and universities working on a single theme. Our first target was to find a zeolite for NH3-SCR, that is, zeolite mining. Zeolite AFX, having the same topology of SSZ-16, was found to be the one of the zeolites. SSZ-16 can be synthesized by using an organic structure-directing agent such as 1,1′-tetramethylenebis(1-azonia-4-azabicyclo[2.2.2]octane; Dab-4, resulting in the formation of Al-rich SSZ-16 with Si/Al below five. We found that AFX crystallized by use of N,N,N′,N′-tetraethylbicyclo[2.2.2]oct-7-ene-2,3:5,6-dipyrrolidinium ion, called TEBOP in this study, had the same analog as SSZ-16 having Si/Al around six and a smaller particle size than SSZ-16. The AFX demonstrated a high performance for NH3-SCR as the zeolitic support to load a large number of divalent Cu ionic species with high hydrothermal stability.

scholarly journals Constructing Large-Scale Genetic Maps Using an Evolutionary Strategy Algorithm

Genetics ◽  
2003 ◽  
Vol 165 (4) ◽  
pp. 2269-2282
Author(s):  
D Mester ◽  
Y Ronin ◽  
D Minkov ◽  
E Nevo ◽  
A Korol
Keyword(s):  
Discrete Optimization ◽  
High Performance ◽  
Large Scale ◽  
Simulated Data ◽  
Real Data ◽  
Genetic Maps ◽  
Chromosome 1 ◽  
Evolutionary Strategy ◽  
Group A ◽  
The One

Abstract This article is devoted to the problem of ordering in linkage groups with many dozens or even hundreds of markers. The ordering problem belongs to the field of discrete optimization on a set of all possible orders, amounting to n!/2 for n loci; hence it is considered an NP-hard problem. Several authors attempted to employ the methods developed in the well-known traveling salesman problem (TSP) for multilocus ordering, using the assumption that for a set of linked loci the true order will be the one that minimizes the total length of the linkage group. A novel, fast, and reliable algorithm developed for the TSP and based on evolution-strategy discrete optimization was applied in this study for multilocus ordering on the basis of pairwise recombination frequencies. The quality of derived maps under various complications (dominant vs. codominant markers, marker misclassification, negative and positive interference, and missing data) was analyzed using simulated data with ∼50-400 markers. High performance of the employed algorithm allows systematic treatment of the problem of verification of the obtained multilocus orders on the basis of computing-intensive bootstrap and/or jackknife approaches for detecting and removing questionable marker scores, thereby stabilizing the resulting maps. Parallel calculation technology can easily be adopted for further acceleration of the proposed algorithm. Real data analysis (on maize chromosome 1 with 230 markers) is provided to illustrate the proposed methodology.

scholarly journals A Review on the Development of Rotman Lens Antenna

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Shruti Vashist ◽  
M. K. Soni ◽  
P. K. Singhal
Keyword(s):  
High Performance ◽  
Beam Steering ◽  
Phase Error ◽  
Antenna System ◽  
Surveillance Systems ◽  
Electronic Warfare ◽  
Design Concepts ◽  
Low Profile ◽  
True Time ◽  
The One

Rotman lenses are the beguiling devices used by the beamforming networks (BFNs). These lenses are generally used in the radar surveillance systems to see targets in multiple directions due to its multibeam capability without physically moving the antenna system. Now a days these lenses are being integrated into many radars and electronic warfare systems around the world. The antenna should be capable of producing multiple beams which can be steered without changing the orientation of the antenna. Microwave lenses are the one who support low-phase error, wideband, and wide-angle scanning. They are the true time delay (TTD) devices producing frequency independent beam steering. The emerging printed lenses in recent years have facilitated the advancement of designing high performance but low-profile, light-weight, and small-size and networks (BFNs). This paper will review and analyze various design concepts used over the years to improve the scanning capability of the lens developed by various researchers.

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