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Lingyun Cheng - One of the best experts on this subject based on the ideXlab platform.

  • intraocular and Systemic Pharmacokinetics of triamcinolone acetonide after a single 40 mg posterior subtenon application
    Ophthalmology, 2010
    Co-Authors: Lijun Shen, Yiqi Chen, Jia Qu, Lingyun Cheng
    Abstract:

    Purpose To characterize the Pharmacokinetics of triamcinolone acetonide (TA) in aqueous, vitreous, and Systemic circulation after a single subtenon injection. Design Prospective interventional case series. Participants Thirty-six patients (36 eyes) who received a single posterior subtenon injection of TA (40 mg in 0.4 ml). Methods Aqueous, vitreous, and blood samples were obtained at 1-hour, 1-day, 3-day, 5-day, 10-day, 14-day, 21-day, and 28-day time points after the posterior subtenon TA injection. At each time point, there were 3 to 6 eyes (patients). The concentrations of TA in the aqueous, vitreous, and plasma were analyzed using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Main Outcome Measures Triamcinolone acetonide concentration in the samples was measured, and pharmacokinetic parameters were calculated. Results The TA concentration-time profile in aqueous consisted of a fast distribution phase during the first 24 hours and a slow elimination phase thereafter. In contrast, the TA concentration-time profile in vitreous consisted of an absorption phase during the first 24 hours followed by a slow elimination phase. The TA in plasma followed a mono-exponential elimination during the study course. The TA concentration peak time for aqueous and plasma was at 1 hour and 24 hours, for vitreous after subtenon injection. The terminal elimination half-life in aqueous, vitreous, and plasma was 11.8, 17.1, and 25 days, respectively. The integral of the area under the concentration time curve (AUC 0-∞ ) was 862 ng/day/ml for aqueous, 1262 ng/day/ml for vitreous, and 17.4 ng/day/ml for plasma. The total TA exposure to vitreous was 46% more than total TA exposure to the aqueous. The TA concentration in vitreous was 70- to 98-fold higher than that in plasma. Conclusions Posterior subtenon TA application can provide a sustained high local ocular TA level while also resulting in a very low Systemic TA level, which may be well below the normal glucocorticoid level in humans. Financial Disclosure(s) The authors have no proprietary or commercial interest in any materials discussed in this article.

G M Murphy - One of the best experts on this subject based on the ideXlab platform.

  • skin and Systemic Pharmacokinetics of tacrolimus following topical application of tacrolimus ointment in adults with moderate to severe atopic dermatitis
    British Journal of Dermatology, 2009
    Co-Authors: N A Undre, Fergal J Moloney, S Ahmadi, P Stevenson, G M Murphy
    Abstract:

    Summary Background  Systemic exposure to tacrolimus following topical application of tacrolimus ointment is minimal. There are, however, no data on the distribution of tacrolimus in the skin. Objectives  To assess the distribution of tacrolimus in the skin and the Systemic Pharmacokinetics of tacrolimus in adults with moderate to severe atopic dermatitis after first and repeated application of tacrolimus ointment. Methods  We investigated skin distribution of topically applied tacrolimus and Systemic Pharmacokinetics of percutaneously absorbed tacrolimus in adults with atopic dermatitis after topical application of tacrolimus 0·1% ointment twice daily for 2 weeks. Tacrolimus concentrations were assessed in full-thickness skin biopsies and blood samples. Results  Of 14 patients, 11 completed treatment and were analysed. Mean ± SD tacrolimus concentrations in the skin at 24 h after first and last ointment applications were 94 ± 20 and 595 ± 98 ng cm−3, respectively. At 168 h after stopping treatment, values were 97% lower than at 24 h after last application. Tacrolimus concentration decreased with increasing skin depth. Systemic tacrolimus exposure after ointment application was low and highly variable, with 31% of samples below the limit of quantification (0·025 ng mL−1) and 94% below 1 ng mL−1. Blood concentrations at 24 h after the first and last ointment applications were 750 and 1800 times lower, respectively, than those in skin. Physicians’ assessments showed that tacrolimus ointment was effective and well tolerated. Conclusions  Tacrolimus was primarily partitioned in the skin, with minimal Systemic absorption after topical application, in patients with atopic dermatitis.

John H. Rodman - One of the best experts on this subject based on the ideXlab platform.

  • Systemic Pharmacokinetics and cellular pharmacology of zidovudine in human immunodeficiency virus type 1 infected women and newborn infants
    The Journal of Infectious Diseases, 1999
    Co-Authors: John H. Rodman, Brian L. Robbins, Patricia M. Flynn, Eleanor Jimenez, Arlene Bardeguez, Jose F Rodriguez, Suzette Blanchard, Arnold Fridland
    Abstract:

    Systemic and intracellular Pharmacokinetics of zidovudine were determined for 28 human immunodeficiency virus type 1-infected pregnant women and their newborn infants. Plasma zidovudine and intracellular zidovudine monophosphate and triphosphate concentrations were determined in serial maternal samples and cord blood at delivery. Higher levels of cord blood zidovudine were associated with lower maternal zidovudine clearance and longer infusion times. Median levels of zidovudine monophosphate and triphosphate in maternal (1556 and 67 fmol/10 6 cells) and cord (1464 and 70 fmol/10 6 cells) blood were similar but highly variable. Intersubject pharmacokinetic variability for zidovudine is substantial, but intravenous therapy provides plasma concentrations and intracellular zidovudine triphosphate levels consistent with high antiviral activity. The substantial amount of intracellular zidovudine triphosphate in cord blood provides an explanation for the clinical success of zidovudine in reducing vertical transmission. Studies of simpler oral regimens of zidovudine can now be evaluated regarding the ability to achieve these pharmacologic end points associated with highly effective parenteral therapy.

  • A Systemic and cellular model for zidovudine plasma concentrations and intracellular phosphorylation in patients.
    The Journal of Infectious Diseases, 1996
    Co-Authors: John H. Rodman, Brian L. Robbins, Patricia M. Flynn, Arnold Fridland
    Abstract:

    In a pharmacokinetic model for the Systemic and cellular disposition of zidovudine in patients, serial measurements of plasma zidovudine and intracellular metabolites were used to simultaneously characterize Systemic Pharmacokinetics and intracellular phosphorylation in 6 human immunodeficiency virus-infected patients. First-order processes are sufficient to describe zidovudine monophosphate kinetics in peripheral blood mononuclear cells (PBMC), and the pharmacokinetic model provided reliable parameter estimates for each subject. The amount of zidovudine monophosphate in PBMC was inversely correlated with plasma zidovudine concentrations, and patients with higher Systemic clearance had less intracellular zidovudine monophosphate. Zidovudine triphosphate values were measurable but not different at each time point. Lower lymphocyte counts were associated with higher intracellular zidovudine monophosphate but lower zidovudine triphosphate. The pharmacokinetic model proposed provides a quantitative link between Systemic zidovudine concentrations and zidovudine monophosphate in PBMC from patients that will be useful in evaluating alternative therapeutic strategies.

Christopher J.h. Porter - One of the best experts on this subject based on the ideXlab platform.

  • Inhalational Administration Patients: Targeting Advantage of Methanesulfonate in Cystic Fibrosis of Inhaled and Intravenous Colistin Pulmonary and Systemic Pharmacokinetics
    2020
    Co-Authors: Michelle Paula Mcintosh, E. Williams, Christopher J.h. Porter, L Roger, Michael J. Dooley, Johnson George, D. Clark, W. S. Yapa, Jian Li, Kashyap Patel
    Abstract:

    Published Ahead of Print 18 February 2014. 10.1128/AAC.01705-13. 2014, 58(5):2570. DOI: Antimicrob. Agents Chemother. Nation and Michelle P. McIntosh Poole, Elyssa Williams, Christopher J. H. Porter, Roger L. Michael J. Dooley, Johnson George, Denise Clark, Susan Shalini W. S. Yapa, Jian Li, Kashyap Patel, John W. Wilson, Inhalational Administration Patients: Targeting Advantage of Methanesulfonate in Cystic Fibrosis of Inhaled and Intravenous Colistin Pulmonary and Systemic Pharmacokinetics

  • molecular weight hydrodynamic volume dictates the Systemic Pharmacokinetics and tumour disposition of polypeg star polymers
    Nanomedicine: Nanotechnology Biology and Medicine, 2015
    Co-Authors: Song Yang Khor, Christopher J.h. Porter, Jinming Hu, Victoria M Mcleod, John F Quinn, Mark Williamson, Michael R Whittaker, Lisa M Kaminskas, Thomas P Davis
    Abstract:

    Abstract Herein we report for the first time the biological fate of poly[(oligoethylene glycol) acrylate] (POEGA) star polymers synthesised via a versatile arm-first reversible addition-fragmentation chain transfer (RAFT) polymerisation approach. The biopharmaceutical behaviour of three different molecular weight (49, 64 and 94kDa) POEGA stars was evaluated in rats and nude mice bearing human MDA MB-231 tumours after intravenous administration. The 94kDa star polymer exhibited a longer plasma exposure time than the 49kDa or 64kDa star polymer; an observation attributable to differences in the rates of both polymer biodegradation and urinary excretion. Tumour biodistribution also correlated with molecular weight and was greatest for the longest circulating 94kDa star. Different patterns of liver and spleen biodistribution were observed between mice and rats for the different sized polymers. The polymers were also well-tolerated in vivo and in vitro at therapeutic concentrations. From the Clinical Editor Advances in nanotechnology has enabled scientists to produce nanoparticle as drug carriers in cancer therapeutics. In this article, the authors studied the biological fate of poly[(oligoethylene glycol) acrylate] (POEGA) star polymers of different size, after intravenous injections. This would allow the subsequent comparison to other drug delivery systems for better drug delivery.

  • pulmonary and Systemic Pharmacokinetics of inhaled and intravenous colistin methanesulfonate in cystic fibrosis patients targeting advantage of inhalational administration
    Antimicrobial Agents and Chemotherapy, 2014
    Co-Authors: Shalini Wickramaratne Senarath Yapa, E. Williams, Michael J. Dooley, Johnson George, D. Clark, Jian Li, Kashyap Patel, John W. Wilson, Susan G. Poole, Christopher J.h. Porter
    Abstract:

    The purpose of this study was to define the pulmonary and Systemic Pharmacokinetics of colistin methanesulfonate (CMS) and formed colistin following intravenous (i.v.) and inhaled administration in cystic fibrosis (CF) patients. Six CF subjects were administered nebulized CMS doses of 2 and 4 million IU and an i.v. CMS infusion of 150 mg of colistin base activity. Blood plasma, sputum, and urine samples were collected for 12 to 24 h postdose. To assess the tolerability of the drug, lung function tests, blood serum creatinine concentrations, and adverse effect reports were recorded. All doses were well tolerated in the subjects. The pharmacokinetic parameters for CMS following i.v. delivery were consistent with previously reported values. Sputum concentrations of formed colistin were maintained at <1.0 mg/liter for 12 h postdose. Nebulization of CMS resulted in relatively high sputum concentrations of CMS and formed colistin compared to those resulting from i.v. administration. The Systemic availability of CMS was low following nebulization of 2 and 4 million IU (7.93% ± 4.26% and 5.37% ± 1.36%, respectively), and the plasma colistin concentrations were below the limit of quantification. Less than 2 to 3% of the nebulized CMS dose was recovered in the urine samples in 24 h. The therapeutic availability and drug targeting index for CMS and colistin following inhalation compared to i.v. delivery were significantly greater than 1. Inhalation of CMS is an effective means of targeting CMS and formed colistin for delivery to the lungs, as high lung exposure and minimal Systemic exposure were achieved in CF subjects.

  • Pulmonary and Systemic Pharmacokinetics of inhaled and intravenous colistin methanesulfonate in cystic fibrosis patients: targeting advantage of inhalational administration
    Antimicrobial Agents and Chemotherapy, 2014
    Co-Authors: Shalini Wickramaratne Senarath Yapa, E. Williams, Michael J. Dooley, Johnson George, D. Clark, Jian Li, Kashyap Patel, John W. Wilson, Susan G. Poole, Christopher J.h. Porter
    Abstract:

    The purpose of this study was to define the pulmonary and Systemic Pharmacokinetics of colistin methanesulfonate (CMS) and formed colistin following intravenous (i.v.) and inhaled administration in cystic fibrosis (CF) patients. Six CF subjects were administered nebulized CMS doses of 2 and 4 million IU and an i.v. CMS infusion of 150 mg of colistin base activity. Blood plasma, sputum, and urine samples were collected for 12 to 24 h postdose. To assess the tolerability of the drug, lung function tests, blood serum creatinine concentrations, and adverse effect reports were recorded. All doses were well tolerated in the subjects. The pharmacokinetic parameters for CMS following i.v. delivery were consistent with previously reported values. Sputum concentrations of formed colistin were maintained at

  • the impact of molecular weight and peg chain length on the Systemic Pharmacokinetics of pegylated poly l lysine dendrimers
    Molecular Pharmaceutics, 2008
    Co-Authors: Lisa M Kaminskas, Benjamin James Boyd, Peter Karellas, Guy Yeoman Krippner, Romina Lessene, Brian D Kelly, Christopher J.h. Porter
    Abstract:

    The impact of PEGylation on the Pharmacokinetics and biodistribution of 3H-labeled poly l-lysine dendrimers has been investigated after intravenous administration to rats. The volumes of distribution, clearance and consequently the plasma half-lives of the PEGylated dendrimers were markedly dependent on the total molecular weight of the PEGylated dendrimer, but were not specifically affected by the PEG chain length alone. In general, the larger dendrimer constructs (i.e. >30 kDa) had reduced volumes of distribution, were poorly renally cleared and exhibited extended elimination half-lives (t1/2 1–3 days) when compared to the smaller dendrimers (i.e. <20 kDa) which were rapidly cleared from the plasma principally into the urine (t1/2 1–10 h). At later time points the larger dendrimers concentrated in the organs of the reticuloendothelial system (liver and spleen); however, the absolute extent of accumulation was low. Size exclusion chromatography of plasma and urine samples revealed that the PEGylated dend...

David N Taylor - One of the best experts on this subject based on the ideXlab platform.

  • Systemic Pharmacokinetics of rifaximin in volunteers with shigellosis
    Antimicrobial Agents and Chemotherapy, 2008
    Co-Authors: David N Taylor, Robin Mckenzie, Anna P Durbin, Colleen Carpenter, Robert Haake, Louis A Bourgeois
    Abstract:

    Rifaximin is an oral antibiotic indicated for treatment of traveler's diarrhea. Rifaximin Pharmacokinetics were evaluated in individuals challenged with Shigella flexneri. Peak plasma rifaximin concentrations were low after nine consecutive doses, and no accumulation was observed. Rifaximin serum levels were minimal and similar to those previously reported in studies of healthy volunteers.

  • Systemic Pharmacokinetics of rifaximin rfx in subjects with shigellosis
    Clinical Pharmacology & Therapeutics, 2005
    Co-Authors: C B Trapnell, David N Taylor, Robert Haake, C Montgomery, D Bettenhausen, Helen S Pentikis
    Abstract:

    Background Rifaximin (RFX) is a non-Systemic (F <0.4%), gut-selective rifamycin SV antimicrobial agent recently approved for the treatment of travelers' diarrhea. This study was done to evaluate the Systemic PK of RFX given to subjects with Shigella flexneri diarrhea. Methods The study was a single-site, open-label PK and safety study of RFX 200 mg given every 8 hours for 9 doses. Subjects were challenged with S. flexneri and subsequently treated with RFX if a standard definition of diarrhea was met. Blood samples were taken for RFX PK with the 3rd and 9th doses of RFX administered under fasting conditions. Results Fifteen subjects were enrolled; 13 developed diarrhea, received RFX and were evaluable for PK and safety. RFX was well tolerated; no significant adverse events were reported. The table below shows the mean (±SD) RFX PK parameters. Mean, dose-normalized parameters from a separate single-dose study in fasted healthy subjects are also shown for the sake of comparison: Conclusions Systemic RFX exposure was low and variable in the subjects with shigellosis. The PK and safety of RFX in patients with diarrhea caused by S. flexneri were comparable to those in healthy volunteers. These results are consistent with previously reported RFX PK (F <0.4%) and safety data. Clinical Pharmacology & Therapeutics (2005) 77, P60–P60; doi: 10.1016/j.clpt.2004.12.118 Table 1.    3rd dose RFX 200 mg 9th dose RFX 200 mg Single dose RFX 200 mg Cmax (ng/mL) 1.63 ± 0.86 1.23 ± 0.52 1.9 AUC0-last (ng*hr/mL) 6.95 ± 5.15 7.83 ± 4.94 9.2 Tmax (hr) 2.77 ± 2.24 2.11 ± 1.58 1.21

  • Systemic Pharmacokinetics of rifaximin (RFX) in subjects with shigellosis
    Clinical Pharmacology & Therapeutics, 2005
    Co-Authors: C B Trapnell, David N Taylor, Robert Haake, C Montgomery, D Bettenhausen, Helen S Pentikis
    Abstract:

    Background Rifaximin (RFX) is a non-Systemic (F