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Luis A Serrano, Ye Yang, Elisa Salvati, Francesco Stellacci, Silke Krol, Stefan Guldin
At present, drug dosage is based on standardised approaches that disregard pharmakokinetic differences between patients and lead to non-optimal efficacy and unnecessary side effects. In this work, we demonstrate the potential of pH-mediated fluorescence spectroscopy for therapeutic drug monitoring in complex media. We apply this principle to the simultaneous quantification of the chemotherapeutic prodrug Irinotecan and its active metabolite SN-38 from human plasma across the clinically relevant concentration range, i...
February 6, 2018: Chemical Communications: Chem Comm
Stefan Stamenković, Aleksandra Pavićević, Miloš Mojović, Ana Popović-Bijelić, Vesna Selaković, Pavle Andjus, Goran Bačić
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting the motor pathways of the central nervous system. Although a number of pathophysiological mechanisms have been described in the disease, post mortem and animal model studies indicate blood-brain barrier (BBB) disruption and elevated production of reactive oxygen species as major contributors to disease pathology. In this study, the BBB permeability and the brain tissue redox status of the SOD1(G93A) ALS rat model in the presymptomatic (preALS) and symptomatic (ALS) stages of the disease were investigated by in vivo EPR spectroscopy using three aminoxyl radicals with different cell membrane and BBB permeabilities, Tempol, 3-carbamoyl proxyl (3CP), and 3-carboxy proxyl (3CxP)...
March 31, 2017: Free Radical Biology & Medicine
Akimitsu Miyauchi
Teriparatide(recombinant human PTH1-34, 20 μg daily subcutaneous injection)has been approved for osteoporosis patients at high risk of fracture in many countries including Japan. Teriparatide daily injection therapy has been reported to increase BMD, improve microarchitecture of bone, and reduce the risk of new vertebral fractures and that of non-vertebral fractures. Pharmakokinetic(PK)study after a single Teriparatide injection of the daily dose in healthy Japanese postmenopausal women(n=18)revealed very rapid achievement of peak blood level(median of tmax=0...
2016: Clinical Calcium
Christoph Driessen, Marianne Kraus, Markus Joerger, Hilde Rosing, Jürgen Bader, Felicitas Hitz, Catherine Berset, Alexandros Xyrafas, Hanne Hawle, Gregoire Berthod, Hermann S Overkleeft, Christiana Sessa, Alwin Huitema, Thomas Pabst, Roger von Moos, Dagmar Hess, Ulrich J M Mey
Downregulation of the unfolded protein response mediates proteasome inhibitor resistance in multiple myeloma. The Human Immunodeficieny Virus protease inhibitor nelfinavir activates the unfolded protein response in vitro. We determined dose-limiting toxicity and recommended dose for phase II of nelfinavir in combination with the proteasome inhibitor bortezomib. Twelve patients with advanced hematologic malignancies were treated with nelfinavir (2500-5000 mg/day p.o., days 1-14, 3+3 dose escalation) and bortezomib (1...
March 2016: Haematologica
Carsten Stoetzer, Andreas Leffler, Jörg Filitz
Patients with opioid pretreatment can be divided into different groups.While patients after successful drug addiction treatment with or without drug replacement therapy usually not require an extensive perioperative pain therapy, patients with persistent chronic pain and patients with an existing opioid addiction regularly are challenging for the anesthetist. Important pathophysiological issues among the patients include opioid tolerance, opioid-induced hyperalgesia (OIH) as well as acute withdrawal symptomes...
February 2015: Anästhesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie: AINS
E M Zeidler, A E Goetz, C Zöllner
BACKGROUND: Pharmacogenetics deals with hereditary factors which influence the pharmacodynamics and pharmacokinetics of drugs leading to individual diverse reactions. Also in anesthesiology differences in the pharmacogenetics of patients can lead to relevant alterations in the pharmacodynamics of drugs. AIM: This article provides a summary of polymorphisms relevant to commonly used anesthetic agents and the clinical relevance in patients treated with these compounds...
November 2013: Der Anaesthesist
H Zerbe, V Luckow, W Cawello, G Cordes
To achieve a fast onset and a sufficiently long duration of action in the long-term treatment of angina pectoris a composite dosage form was developed, consisting of a fast-release initial dose Di and a slow-release maintenance dose Dm. The product is designed to be given once daily in the morning to achieve sufficiently high blood levels for clinical response during day-time with declining blood levels during night-time to avoid tolerance. In view of its pharmacokinetic properties, the antianginal drug isosorbide-5-nitrate (IS-5-N) was selected as the model substance...
January 1985: Pharmaceutical Research
Ritz, Schömig
The main indications for diuretic treatment of renal patients are edema and hypertension. Pharmakokinetics and pharmacodynamics of diuretics are altered in patients with proteinuria and/or impaired renal function. These patients exhibit avid sodium retention. Diuretics are partially inactivated by binding to proteins in tubular fluid. The natriuretic response to diuretics is limited by counter-regulation, specifically increased proximal tubular reabsorption in response to hypovolemia and increased distal tubular sodium reabsorption in response to increased sodium load...
June 1, 2000: Therapeutische Umschau. Revue Thérapeutique
Yoshio Shimizu, Yasuhiko Tomino
No abstract text is available yet for this article.
2012: Nihon Jinzo Gakkai Shi
Natalícia De Jesus Antunes, Ricardo Carvalho Cavalli, Maria Paula Marques, Vera Lucia Lanchote
Metoprolol is available for clinical use as a racemic mixture. The S-(-)-metoprolol enantiomer is the one expressing higher activity in the blockade of the β(1)-adrenergic receptor. The α-hydroxymetoprolol metabolite also has activity in the blockade of the β(1)-adrenergic receptor. The present study describes the development and validation of a stereoselective method for sequential analysis of metoprolol and of α-hydroxymetoprolol in plasma using high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS)...
January 2013: Chirality
Focke Ziemssen, Heinrich Heimann
INTRODUCTION: The benzoporphyrine derivative verteporfin has lost its importance to the treatment of the most frequent neovascular eye diseases. Nevertheless, it is still mandatory to define the remaining applications, role, and potential of verteporfin in ocular photodynamic therapy (PDT), including the dosages of administration, effectiveness, and safety profile. AREAS COVERED: Although verteporfin PDT has forfeited the first-line status and value of treating subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration or pathologic myopia, the treatment remains the standard of care for choroidal haemangioma and polypoidal choroidal vasculopathy...
August 2012: Expert Opinion on Drug Metabolism & Toxicology
U Plöckinger
This paper outlines the present status of medical therapy of acromegaly. Indications for permanent postoperative treatment, postirradiation treamtent to bridge the interval until remission as well as primary medical therapy are elaborated. Therapeutic efficacy of the different available drugs-somatostatin receptor ligands (SRLs), dopamine agonists, and the GH antagonist Pegvisomant-is discussed, as are the indications for and efficacy of their respective combinations. Information on their mechanism of action, and some pharmakokinetic data are included...
2012: International Journal of Endocrinology
H Dorchy
The principal aims of therapeutic management of the child, adolescent and adult with type 1 diabetes are to allow good quality of life and to avoid long-term complications by maintaining blood glucose concentrations close to the normal range and an HbA1c level under 7%. The number of daily insulin injections, 2 or > or =4 or pumps, by itself does not necessarily give better results, but the 4-injection regimen allows greater freedom, taking into account that the proper insulin adjustment is difficult before adolescence...
2006: Revue Médicale de Bruxelles
Harry Dorchy
The principal aims of therapeutic management of the child, adolescent and adult with type 1 diabetes are to allow good quality of life and to avoid long-term complications by maintaining blood glucose concentrations close to the normal range and an HbA1c level under 7%. The number of daily insulin injections, 2 or > or = 4, by itself does not necessarily give better results, but the 4-injection regimen allows greater freedom, taking into account that the proper insulin adjustment is difficult before adolescence...
2010: Revue Médicale de Bruxelles
Martin L Neitzel, Danielle L Aubele, Jennifer L Marugg, Jacek J Jagodzinski, Andrei W Konradi, Michael A Pleiss, Balazs Szoke, Wes Zmolek, Erich Goldbach, Kevin P Quinn, John-Michael Sauer, Elizabeth F Brigham, William Wallace, Michael P Bova, Susanna Hemphill, Guriqbal Basi
Herein we describe the structure-activity relationship (SAR) of amino-caprolactam analogs derived from amino-caprolactam benzene sulfonamide 1, highlighting affects on the potency of γ-secretase inhibition, selectivity for the inhibition of APP versus Notch processing by γ-secretase and selected pharmakokinetic properties. Amino-caprolactams that are efficacious in reducing the cortical Aβ(x-40) levels in FVB mice via a single 100 mpk IP dose are highlighted.
June 15, 2011: Bioorganic & Medicinal Chemistry Letters
C Prenant, C Cawthorne, M Fairclough, N Rothwell, H Boutin
IL-1RA is a naturally occurring antagonist of the pro-inflammatory cytokine interleukin-1 (IL-1) with high therapeutic promise, but its pharmacokinetic remains poorly documented. In this report, we describe the radiolabeling of recombinant human interleukin-1 receptor antagonist (rhIL-1RA) with fluorine-18 to allow pharmacokinetic studies by positron emission tomography (PET). rhIL-1RA was labeled randomly by reductive alkylation of free amino groups (the epsilon-amino group of lysine residues or amino-terminal residues) using [(18)F]fluoroacetaldehyde under mild reaction conditions...
September 2010: Applied Radiation and Isotopes
Anastasia Karioti, Anna Rita Bilia
70 years have passed since the first isolation of the naphthodianthrones hypericin and pseudohypericin from Hypericum perforatum L. Today, they continue to be one of the most promising group of polyphenols, as they fascinate with their physical, chemical and important biological properties which derive from their unique chemical structure. Hypericins and their derivatives have been extensively studied mainly for their antitumor, antiviral and antidepressant properties. Notably, hypericin is one of the most potent naturally occurring photodynamic agents...
2010: International Journal of Molecular Sciences
Lisa Yon, Brian Faulkner, Sumolya Kanchanapangka, Narongsak Chaiyabutr, Sompast Meepan, Bill Lasley
Noninvasive hormone assays provide a way to determine an animal's health or reproductive status without the need for physical or chemical restraint, both of which create unnecessary stress for the animal, and can potentially alter the hormones being measured. Because hormone metabolism is highly species-specific, each assay must be validated for use in the species of interest. Validation of noninvasive steroid hormone assays has traditionally required the administration of relatively high doses of radiolabelled compounds (100 µCi or more of (14)C labeled hormone) to permit subsequent detection of the excreted metabolites in the urine and feces...
November 2010: Zoo Biology
U Müller-Werdan, J Wilhelm, S Hettwer, S Nuding, H Ebelt, K Werdan
This article deals with specific aspects of the patient with sepsis and his treatment. With adequate therapy (antibiotics started within the first hour, early goal-directed therapy) initiated as early as possible, the patient with community-aquired severe sepsis in the emergency department has a considerable better chance to survive than the patient with prolonged severe sepsis in the ICU. The average age of patients with severe sepsis and septic shock treated at the ICU is rising, with consequences like oligosymptomatic presentation, altered pharmakokinetics according to older-age-induced reduced organ functions and prolonged stay at the ICU due to comorbidity...
July 2009: Der Internist
András Sümegi
Atypical antipsychotics are now widely used in the acute and long-term treatment in bipolar disorder. The role of atypical antipsychotics as acute agents, add-on medications; or as primary mood stabilizers in different phases of bipolar disorder is an important current research tendency. However, in bipolar disorder the mostly used indication of quetiapine is the management of acute manic phases, clinical data and the actual research results suggest that it may have both antidepressant and long-term antimanic effects...
December 2008: Neuropsychopharmacologia Hungarica
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