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Pulmonary pharmacokinetics hplc

Kyungsoo Oh, Moon-Chang Baek, Wonku Kang
Sulfisoxazole (SFX) is still used in combination with trimethoprim in cattle despite adverse drug reactions (e.g., urolithiasis). Recently, SFX is known to be a promising repositioned drug candidate for pulmonary hypertension and cancer. We developed a simultaneous determination method of SFX and its N-acetylated metabolites (N(1)-acetyl SFX, N1AS; N(4)-acetyl SFX, N4AS; diacetyl SFX, DAS) using HPLC-MS/MS for the first time, and examined the pharmacokinetics of SFX in mice. N1AS and DAS were converted rapidly to SFX and N4AS, respectively, in mouse plasma...
September 10, 2016: Journal of Pharmaceutical and Biomedical Analysis
Bianca Maria Goffredo, Sara Cairoli, Alessia Vitale, Tiziana Corsetti, Anna Pastore
Sildenafil is a selective inhibitor of cGMP-specific type 5 phosphodiesterase (PDE5) used for the treatment of Pulmonary Arterial Hypertension (PAH) in the adults. In pediatrics, PAH treatment options include the off-label use of sildenafil. Sildenafil is metabolized in the liver by cytocrome P450 into its active metabolite, N-desmethyl sildenafil. The determination of plasma levels of sildenafil and N-desmethyl sildenafil could be useful for therapy optimization and pharmacokinetic studies. We have developed and validated a method for the quantification of sildenafil and its metabolite in plasma of children by rapid extraction, using High Performance Liquid Chromatography (HPLC) with ultraviolet (UV) detection...
May 23, 2016: Biomedical Chromatography: BMC
Ying Jing, Li Qin Zhu, Jian Wei Yang, Shu Ping Huang, Qian Wang, Jie Zhang
Rifampicin (RIF) induces cytochrome P450, which in turn catalyzes drug metabolism; however, pharmacokinetic studies on this phenomenon in the Chinese population, especially in the context of disease, are limited. Therefore, we sought to establish population-based pharmacokinetic models of RIF in a Chinese population with pulmonary tuberculosis (TB). Clinical data were retrospectively collected from 54 patients with pulmonary TB and analyzed alongside RIF blood levels from 95 samples collected prior to RIF administration and between 2 and 12 hours after treatment...
May 2016: Journal of Clinical Pharmacology
Lucila Garcia Contreras, Jean Sung, Mariam Ibrahim, Katharina Elbert, David Edwards, Anthony Hickey
Tuberculosis (TB) is a life-threatening infection that requires a lengthy treatment process that is often associated with adverse effects. Pulmonary delivery of anti-TB drugs has the potential to increase efficacy of treatment by increasing drug concentrations at the lungs, the primary site of infection. The aim of the present study is to evaluate the disposition of rifampicin (RIF) after its pulmonary administration as porous particles (PPs) to guinea pigs and contrast it to that after oral administration...
August 3, 2015: Molecular Pharmaceutics
Christine Sekaggya Wiltshire, Mohammed Lamorde, Alexandra Scherrer, Joseph Musaazi, Natascia Corti, Buzibye Allan, Rita Nakijoba, Damalie Nalwanga, Lars Henning, Amrei Von Braun, Solome Okware, Barbara Castelnuovo, Andrew Kambugu, Jan Fehr
INTRODUCTION: There is limited data available on exposure to anti-tuberculosis (TB) drugs in this region. Peloquin has described reference ranges [1] however some studies have demonstrated that patients actually achieve concentrations below these ranges [2]. There is limited data about exposure to anti-TB drugs in the HIV/TB co-infected population in Sub-Saharan Africa. Our objective is to describe the concentration of anti-TB drug levels in a well characterized prospective cohort of adult patients starting treatment for pulmonary TB...
2014: Journal of the International AIDS Society
Andrea Calcagno, Lorena Baietto, Nicole Pagani, Marco Simiele, Sabrina Audagnotto, Antonio D'Avolio, Francesco Giuseppe De Rosa, Giovanni Di Perri, Stefano Bonora
AIM: To investigate the pharmacokinetics of voriconazole when administered to HIV-positive patients receiving treatment with atazanavir-containing therapies according to CYP2C19 genotype. MATERIALS & METHODS: We describe four HIV-positive patients with pulmonary aspergillosis treated with voriconazole and atazanavir-based regimens (with or without ritonavir). They were managed by assessing their CYP2C19 genotype (CYP2C19*2, rs4244285, G>A, real-time PCR) and therapeutic drug monitoring (HPLC-based validation methods)...
July 2014: Pharmacogenomics
Yoshiaki Ohtsu, Fumiyo Takanuki, Yasuhisa Fukunaga, Kiyoshi Noguchi
The potent phosphodiesterase 4 inhibitor ASP3258 contains a carboxylic acid moiety and a naphthyridine ring and is a novel therapeutic agent for asthma and chronic obstructive pulmonary disease. To support the drug development of ASP3258, we developed and validated a simple method for its determination in rat plasma. Following the addition of the analog AS1406604-00 as an internal standard, plasma samples were processed using C18 -bonded solid-phase extraction cartridges under acidic conditions and injected into a high-performance liquid chromatography system with fluorescence detection...
February 2015: Biomedical Chromatography: BMC
Paul Gavra, Anne Q-N Nguyen, Yves Theoret, Catherine Litalien, André Y Denault, France Varin
BACKGROUND: Milrinone administered through inhalation is an emerging method aimed at specifically reducing pulmonary hypertension without affecting systemic pressures. Its administration has been shown to be useful both in patients undergoing cardiac surgery and for persistent pulmonary hypertension of the newborn. These populations are prone to receive many concomitant medications and/or blood sampling may require a low volume quantification method. To address these issues in view of pharmacokinetic studies, this article aims to develop and validate a specific and sensitive analytical assay using high performance liquid chromatography (HPLC) and tandem mass spectrometry (MS/MS) detection for the quantification of milrinone plasma concentrations after inhalation in patients undergoing cardiac surgery...
October 2014: Therapeutic Drug Monitoring
Chunmei Liu, Jing Shi, Qingyun Dai, Xiaoxing Yin, Xiaoyan Zhang, Aiping Zheng
OBJECTIVE: The aim of this study was to investigate the ciprofloxacin liposome of high encapsulation efficiency with optimal physical properties for pulmonary administration and to test its in-vivo potential in rats. METHODS: Ciprofloxacin-loaded liposome was prepared by gradient of ammonium sulfate method. The particle size and morphology were determined using a NANOPHOX particle size analyzer and a transmission electron microscope, respectively. Encapsulation efficiency was calculated by UV spectrophotometry...
February 2015: Drug Development and Industrial Pharmacy
Shaheen Sultana, Aseem Bhatnagar, Harish Rawat, Dhruv Kumar Nishad, Sushma Talegaonkar, Farhan Jalees Ahmad, Gaurav Mittal
CONTEXT: Medical management of heavy metal toxicity including radioactive ones is the cause of concern because of their increased use in energy production, healthcare and mining. As inhalation is one of the primary routes for internalization, a formulation is needed to trap metal(s) at the portal of entry itself. OBJECTIVE: Objective was to formulate and characterize a nanonized dry powder inhaler (DPI) formulation of alendronate sodium as potential inhalable antidote for chelating metal toxicants...
August 2014: Pharmaceutical Development and Technology
Wei Hu, Chao Zhang, Wenjin Hu, Yun Fang, Wenjie Hou
Aerosol delivery is a route which is advantageous to the therapy of pulmonary diseases, such as lung cancer. The pharmacokinetics and tissue distribution after aerosol delivery of carboxylate form of hydroxycamptothecin (C-HCPT) were investigated. The concentrations of the three different types (lactone, carboxylate and the total of both forms) of HCPT were measured by HPLC analysis. The initial experiment showed no evident difference between lactone and carboxylate in the lungs during the aerosol treatment, compared with the HCPT content in plasma...
October 2012: Fitoterapia
Rahul Kumar Verma, Jatinder Kaur Mukker, Ravi Shankar Prasad Singh, Kaushlendra Kumar, Priya Ranjan Prasad Verma, Amit Misra
Dry powder inhalations (DPI) of microparticles containing isoniazid (INH) and rifabutin (RFB) are under preclinical development for use in pulmonary tuberculosis. Microparticles containing 0.25, 2.5, or 25 mg of each drug were administered daily for 90 days to rhesus macaques (n = 4/group). Single inhalations or intravenous (i.v.) doses were administered to separate groups. Drugs in serum, alveolar macrophages, and organ homogenates were assayed by high-performance liquid chromatography (HPLC). The RFB/INH in the lungs (101...
April 2, 2012: Molecular Pharmaceutics
Maysa Suyagh, Ahmed F Hawwa, Paul S Collier, Jeffrey S Millership, Prashant Kole, Muriel Millar, Mike D Shields, Henry L Halliday, James C McElnay
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Little is known about the pharmacokinetics of potassium canrenoate/canrenone in paediatric patients WHAT THIS STUDY ADDS: A population pharmacokinetic model has been developed to evaluate the pharmacokinetics of canrenone in paediatric patients who received potassium canrenoate as part of their therapy in the intensive care unit. AIMS To characterize the population pharmacokinetics of canrenone following administration of potassium canrenoate to paediatric patients...
November 2012: British Journal of Clinical Pharmacology
Emmanuel Boselli, Dominique Breilh, Aurore Caillault-Sergent, Sarah Djabarouti, Christian Guillaume, Fabien Xuereb, Lionel Bouvet, Thomas Rimmelé, Marie-Claude Saux, Bernard Allaouchiche
OBJECTIVES: This study aimed to determine the steady-state serum and alveolar concentrations of linezolid administered by continuous infusion to critically ill patients with ventilator-associated pneumonia (VAP). PATIENTS AND METHODS: This was a prospective, open-label study performed in an intensive care unit and research ward in a university hospital. Twelve critically ill adult patients with VAP received 600 mg of linezolid as a loading dose followed by 1200 mg/day by continuous infusion...
May 2012: Journal of Antimicrobial Chemotherapy
Abida Shaheen, Muzammil Hasan Najmi, Waseem Saeed, Zia-Ur-Rehman Farooqi
BACKGROUND: This clinical study investigated the pharmacokinetics of standard doses of rifampicin (RMP; 450 and 600 mg) in pulmonary tuberculosis (TB) patients in the context of its high sterilizing potential and the increased frequency of multidrug-resistant TB in Pakistan. The objective of this study was to determine the sufficiency or inadequacy of peak plasma levels of RMP in pulmonary TB patients after the administration of standard doses. METHODS: Twenty adult patients with newly diagnosed pulmonary TB consented to participate in the study...
June 2012: Scandinavian Journal of Infectious Diseases
David P Nicolau, Christina Sutherland, Donna Winget, Robert P Baughman
While previous reports have described the bronchopulmonary profile of the fluoroquinolones in healthy volunteers, limited data are available in infected patients. The purpose of this study was to determine the intrapulmonary profile of high-dose (750 mg) levofloxacin in patients during an acute exacerbation of chronic bronchitis (AECB). Twenty-four patients experiencing clinical signs and symptoms of AECB were enrolled. Once enrolled, patients received levofloxacin 750 mg once daily × 5 days. Bronchoalveolar lavage aspirates and simultaneous plasma samples were obtained at 4 h, 12 h or 24 h after the third dose...
February 2012: Pulmonary Pharmacology & Therapeutics
C Tsagogiorgas, T Jung, J Krebs, B Theisinger, G Beck, B A Yard, M Quintel
Semifluorinated alkanes (SFAs) have been described as potential excipients for pulmonary drug delivery, but proof of their efficacy is still lacking. We tested whether SFA formulations with the test drug ibuprofen can be nebulised and evaluated their pharmacokinetics. Physico-chemical properties of five different ibuprofen formulations were evaluated: an aqueous solution (H2O), two different SFAs (perfluorohexyloctane (F6H8), perfluorobutylpentane (F4H5)) with and without ethanol (SFA/EtOH). Nebulisation was performed with a jet catheter system...
January 17, 2012: International Journal of Pharmaceutics
Jiadao Wan, Libo Zhao, Chuan Xu, Shaohui Zhang, Zhixin Zhang, Cheng Zeng, Mujun Chang, Junhua Xiao, Jialing Wang
Amiodarone, an iodinated benzofuran derivative with predominantly class III anti-arrhythmic effects, is used to treat supraventricular and ventricular arrhythmias. The purpose of this study was to assess the potential of neferine, an effective anti-pulmonary fibrosis drug isolated from the embryo of Nelumbo nucifera Gaertner's seeds, to alter the pharmacokinetic profile of amiodarone. Experimental Sprague-Dawley rats were randomly divided into two groups. In groups 1 and 2, amiodarone was given to rats by intragastric and intravenous administration, respectively, while neferine was co-administratered by intragastric administration...
August 2011: Biomedical Chromatography: BMC
L J Berghaus, S Giguère, T L Sturgill, D Bade, T J Malinski, R Huang
The objectives of this study were to determine the plasma and pulmonary disposition of gamithromycin in foals and to investigate the in vitro activity of the drug against Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) and Rhodococcus equi. A single dose of gamithromycin (6 mg/kg of body weight) was administered intramuscularly. Concentrations of gamithromycin in plasma, pulmonary epithelial lining fluid (PELF), bronchoalveolar lavage (BAL) cells, and blood neutrophils were determined using HPLC with tandem mass spectrometry detection...
February 2012: Journal of Veterinary Pharmacology and Therapeutics
Rüdiger Nave
Ciclesonide (Alvesco(®)) is an inhaled corticosteroid administered as a solution via a metered-dose inhaler, using hydrofluoroalkane HFA-134a as a propellant. Ciclesonide is inhaled as a prodrug, which is activated by pulmonary esterases to the pharmacologically active metabolite desisobutyryl-ciclesonide (des-CIC). Lung deposition is an important factor that contributes to the desired therapeutic effect of inhaled corticosteroid. More than 50% of the inhaled dose is deposited in the lung as demonstrated by scintigraphical methods after inhalation of ciclesonide...
April 2010: Bioanalysis
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