Archive for May, 2008
Thursday, May 1st, 2008
A chemoenzymatic approach to the synthesis of enantiomerically pure (S)-3-hydroxy-gamma-butyrolactone.
Optically pure (S)-3-hydroxy-gamma-butyrolactone, an important chiral building block in the pharmaceutical industry, was synthesized from L: -malic acid by combining a selective hydrogenation and a lipase-catalyzed hydrolysis. Lipase from Candida rugosa was found to be the ...
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Thursday, May 1st, 2008
Caffeine-inducible ATP release is mediated by Ca2+-signal transducing system from the endoplasmic reticulum to mitochondria.
Adenosine triphosphate (ATP) is released as an autocrine/paracrine signal from a variety of cells. The present study was undertaken to clarify the Ca(2+)-signal pathway involved in the caffeine-inducible release of ATP ...
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Thursday, May 1st, 2008
[Emergency physician and AutoPulse - a good duo in preclinical emergency services? : Case example and report on experience.]
Survival rates after cardiac arrest remain poor despite substantial efforts to advance the cardiopulmonary resuscitation algorithm in the last decades. Recent changes in the resuscitation guidelines in ...
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Thursday, May 1st, 2008
Application of gastrointestinal simulation for extensions for biowaivers of highly permeable compounds.
The goal of this study was to apply gastrointestinal simulation technology and integration of physiological parameters to predict biopharmaceutical drug classification. GastroPlus(R) was used with experimentally determined physicochemical and pharmacokinetic drug properties to simulate ...
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Thursday, May 1st, 2008
Use of the biopharmaceutical classification system in early drug development.
The Biopharmaceutics Classification System (BCS) is not only a useful tool for obtaining waivers for in-vivo bioequivalence studies but also for decision making in the discovery and early development of new drugs. Measurement of solubility and ...
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Thursday, May 1st, 2008
Reaction phenotyping: current industry efforts to identify enzymes responsible for metabolizing drug candidates.
Reaction phenotyping studies to identify specific enzymes involved in the metabolism of drug candidates are increasingly important in drug discovery efforts. Experimental approaches used for CYP reaction phenotyping include incubations with cDNA expressed ...
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Thursday, May 1st, 2008
Sodium-coupled Monocarboxylate Transporters in Normal Tissues and in Cancer.
SLC5A8 and SLC5A12 are sodium-coupled monocarboxylate transporters (SMCTs), the former being a high-affinity type and the latter a low-affinity type. Both transport a variety of monocarboxylates in a Na(+)-coupled manner. They are expressed in the gastrointestinal tract, ...
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Thursday, May 1st, 2008
Role of biotransformation studies in minimizing metabolism-related liabilities in drug discovery.
Metabolism-related liabilities continue to be a major cause of attrition for drug candidates in clinical development. Such problems may arise from the bioactivation of the parent compound to a reactive metabolite capable of modifying biological ...
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Thursday, May 1st, 2008
Recent advances in blood-brain barrier disruption as a CNS delivery strategy.
The blood-brain barrier (BBB) is a complex functional barrier composed of endothelial cells, pericytes, astrocytic endfeets and neuronal cells. This highly organized complex express a selective permeability for molecules that bear, amongst other parameters, adequate ...
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Thursday, May 1st, 2008
Pharmacokinetically-guided lead optimization of nitrofuranylamide anti-tuberculosis agents.
In an effort to develop novel and more potent therapies to treat tuberculosis, a new class of chemical agents, nitrofuranylamides, is being developed. The present study examines biopharmaceutic properties and preclinical pharmacokinetics of nitrofuranylamides at early stages of drug ...
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Thursday, May 1st, 2008
Highly variable drugs: observations from bioequivalence data submitted to the FDA for new generic drug applications.
INTRODUCTION: It is widely believed that acceptable bioequivalence studies of drugs with high within-subject pharmacokinetic variability must enroll higher numbers of subjects than studies of drugs with lower variability. We ...
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Thursday, May 1st, 2008
Evaluation of methods for estimating time to steady state with examples from phase 1 studies.
An overview is provided of the methodologies used in determining the time to steady state for Phase 1 multiple dose studies. These methods include NOSTASOT (no-statistical-significance-of-trend), Helmert contrasts, spline (quadratic) regression, ...
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Thursday, May 1st, 2008
Nanoparticles Containing Anti-inflammatory Agents as Chemotherapy Adjuvants: Optimization and In Vitro Characterization.
The pre-administration of dexamethasone (DEX) has previously been shown to enhance the anti-tumor efficacy of chemotherapeutic agents. The delivery of anti-inflammatory agents specifically to tumors via nanoparticle carriers is expected to promote the effectiveness ...
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Thursday, May 1st, 2008
Percutaneous permeation enhancement by terpenes: mechanistic view.
A popular approach for improving transdermal drug delivery involves the use of penetration enhancers (sorption promoters or accelerants) which penetrate into skin to reversibly reduce the barrier resistance. The potential mechanisms of action of penetration enhancers include disruption of ...
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Thursday, May 1st, 2008
Pharmacogenetic and metabolic differences between dog breeds: their impact on canine medicine and the use of the dog as a preclinical animal model.
There is limited information describing species related pharmacogenetic differences in animals. Despite the lack of genetic information in veterinary medicine, breed specific responses ...
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Thursday, May 1st, 2008
FDA critical path initiatives: opportunities for generic drug development.
FDA\'s critical path initiative documents have focused on the challenges involved in the development of new drugs. Some of the focus areas identified apply equally to the production of generic drugs. However, there are scientific challenges unique ...
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Thursday, May 1st, 2008
Prodrug approaches for CNS delivery.
Central nervous system (CNS) drug delivery remains a major challenge, despite extensive efforts that have been made to develop novel strategies to overcome obstacles. Prodrugs are bioreversible derivatives of drug molecules that must undergo an enzymatic and/or chemical transformation in vivo ...
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Thursday, May 1st, 2008
Rheological evaluation of silicon/carbopol hydrophilic gel systems as a vehicle for delivery of water insoluble drugs.
The present study analyzed the thickening properties of Carbopol 974 and 971 in a 50:50 mixture of water/Silsensetrade mark A-21, a new cationic silicon miscible in any proportion with water. ...
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Thursday, May 1st, 2008
A flexible nonlinear feedback system that captures diverse patterns of adaptation and rebound.
An important approach to modeling tolerance and adaptation employs feedback mechanisms in which the response to the drug generates a counter-regulating action which affects the response. In this paper we analyze a family ...
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Thursday, May 1st, 2008
Pharmacokinetics of 1,4-Butanediol in Rats: Bioactivation to gamma-Hydroxybutyric Acid, Interaction with Ethanol, and Oral Bioavailability.
1,4-Butanediol (BD), a substance of abuse, is bioactivated to gamma-hydroxybutyrate (GHB), but its fundamental pharmacokinetics (PK) have not been characterized. Because this bioactivation is partly mediated by alcohol dehydrogenase, we hypothesized ...
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Thursday, May 1st, 2008
Pharmacokinetic Interaction between the Flavonoid Luteolin and gamma-Hydroxybutyrate in Rats: Potential Involvement of Monocarboxylate Transporters.
Monocarboxylate transporter 1 (MCT1) has been previously reported as an important determinant of the renal reabsorption of the drug of abuse, gamma-hydroxybutyrate (GHB). Luteolin is a potent MCT1 inhibitor, inhibiting the ...
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Thursday, May 1st, 2008
The Pharmacokinetics and Interactions of Ivermectin in Humans-A Mini-review.
Ivermectin is an antiparasitic drug with a broad spectrum of activity, high efficacy as well as a wide margin of safety. Since 1987, this compound has a widespread use in veterinary medicine and it use has been ...
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Thursday, May 1st, 2008
Informatic tools and approaches in postmarketing pharmacovigilance used by FDA.
The safety profile of newly approved drugs and therapeutic biologics is less well developed by pre-marketing clinical testing than is the efficacy profile. The full safety profile of an approved product is established during years of ...
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Thursday, May 1st, 2008
Cell cycle checkpoint models for cellular pharmacology of Paclitaxel and platinum drugs.
A pharmacokinetic-pharmacodynamic mathematical model is developed for cellular pharmacology of chemotherapeutic drugs for which the decisive step towards cell death occurs at a point in the cell cycle, presumably corresponding to a cell cycle ...
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Thursday, May 1st, 2008
The Role of Quantitative Pharmacology in an Academic Translational Research Environment.
Translational research is generally described as the application of basic science discoveries to the treatment or prevention of disease or injury. Its value is usually determined based on the likelihood that exploratory or developmental research ...
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