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At least 289 records · Page 16Linked to original sources
PubMed1999

Stereoselective determination of trihexyphenidyl in human serum by LC-ESI-MS.

The antiparkinsonian drug trihexyphenidyl (THP) is currently manufactured and administered as a racemate. However, stereochemistry can play significant role in the drug's pharmacokinetics, biotransformation, metabolism, interaction with cellular and tissue components and overall effect on human body. It is necessary to consider such a drug as a mixture of two compounds (drug enantiomers), with their own effect on the human body. The present paper describes a simple and sensitive LC-MS method for the stereoselective determination of THP in human serum. In this study, the sample was prepared by a solid-phase extraction (SPE) procedure. The enantiomer separation was done using native beta-cyclodextrin stationary phase LC column. The combination of ESI-MS detection and SPE showed excellent sensitivity and selectivity of the method. The limits of detection of <0.1 ng/ml can be easily achieved, which is 7,000 times lower than the detection limits achievable by a UV detection method. The method has at least a 3-order of magnitude linear dynamic range for both enantiomers (concentrations up to 1,323 ng/ml were tested). This is 24 times wider than the therapeutic range of THP (peak THP plasma concentration of 55 ng/ml was previously reported). The recoveries of THP enantiomers from the human serum were > 95%.

Acetic Acid↗
PubMed2002

Update on the management of Helicobacter pylori infection, including drug-resistant organisms.

Helicobacter pylori infection has many different clinical outcomes. Not all infected persons need to be treated. Therefore, indications for treatment have to be clear, and several consensus guidelines have been formulated to aid the medical practitioner in this decision-making process. Triple therapy with a proton pump inhibitor (PPI), in combination with amoxicillin and clarithromycin is the established treatment of choice. For patients with penicillin hypersensitivity, metronidazole can be substituted for amoxicillin. Bacterial resistance to antibiotics is a major factor adversely affecting treatment success. Resistance to metronidazole has been reported in up to 80%, and resistance to clarithromycin in 2-10% of strains cultured. Resistance to either one of the antibiotics has been reported to result in a drop in efficacy of up to 50%. Emergence of resistance to both metronidazole and clarithromycin following failed therapy is a cause for concern; this underlines the need to use the best available first-line therapy. To avoid the emergence of resistance to both key antibiotics, the combination of metronidazole and clarithromycin should be avoided where possible. For failed treatment, several strategies can be employed. These include ensuring better compliance with repeat therapy, and maximizing the efficacy of repeat treatment by increasing dosage and duration of treatment, as well as altering the choice of drugs. Quadruple therapy incorporating a bismuth compound with a PPI, tetracycline and metronidazole has been a popular choice as a "rescue" therapy. Ranitidine bismuth citrate has been shown to be able to overcome metronidazole and clarithromycin resistance; it may be a useful compound drug to use in place of a PPI in "rescue" therapies. In the case of persistent treatment failures, it is useful to consider repeating gastroscopy and obtaining tissue for culture, and then prescribe antibiotics according to bacterial susceptibility patterns. It is also important in refractory cases to review the original indication for treatment and determine the importance of the indication.

Anti-Bacterial Agents↗
PubMed2001

[The Arabic pharmacology and the introduction to Europe: the background of the Arabic pharmacology - the legacy from Greece].

When the Arabic-Islamic medicine evolved partly as a consequence of the wave of translations from mainly Greek medical books to Arabic in the 9th century the pharmacological works, which were available, were also translated. The books of Dioscurides and Galen on pharmacological matters became the decisive books of pharmacological translated literature and they formed the basis of the pharmacological understanding in the subsequent extensive literature on pharmacognosy and pharmacology written in Arabic. Nevertheless the Arabs united these two disciplines in a regular pharmacy and they evolved it as an independent discipline, which although attached to medicine was regarded as having its own praxis. The physicians and scientists rationalized and systematized their knowledge of medicinal plants and drugs and extended their knowledge by using original observations and research. Many books on medicaments were written, both as materia medica, i.e. records on simple drugs, and dispensatories, i.e. books on compounded drugs. These two kinds of books were always written separately as they were seen by the Arabs themselves as pertaining to two different subdisciplines, which meant that they were separated too in independent chapters or books in general Arabic works on medicine. When the extensive translations of Arabic medical literature to Latin took place in Italy and Spain in the 11th and 12th centuries, the Arabic pharmacological literature was of course also translated, and its decisive influence on later medieval European medical writings is easy to demonstrate. In the 18th century Peter Forsskaal was one of the first Europeans in the modern scientific tradition to collect and make notes on drugs used in Cairo and in Yemen.

Arab World↗
PubMed2001

Engineering orthogonal ligand-receptor pairs from "near drugs".

Cell-permeable small molecules are powerful tools for unraveling complex cellular pathways. We demonstrate that nuclear hormone receptors can be engineered through mutagenesis to create orthogonal ligand-receptor pairs to control transcription. Mutated residues in the retinoid X receptor (RXR) were chosen from structural analysis of RXR and the retinoic acid receptor (RAR) ligand binding domains. The potential ligands screened for activation of variant receptors are "near drugs"--compounds synthesized during structure-activity studies that are structurally similar to an approved drug yet inactive on the wild-type receptor. One variant, Q275C;I310M;F313I, is poorly activated by ligands for the wild-type receptor but is activated by a "near drug", fulfilling the criteria of an orthogonal ligand-receptor pair. These experiments demonstrate that nuclear hormone receptors are well suited to supply orthogonal ligand-receptor pairs for experimental biology, biotechnology, and gene therapy. Our findings also demonstrate the general principle that inactive compounds synthesized during drug discovery can be combined with mutant proteins to rapidly create new tools for controlling cellular processes.

Alitretinoin↗
PubMed1980

Drug supplies, management and manufacturing for local needs. The provision of pharmaceuticals by appropriate technology.

The provision of drugs is of much lower importance to poor communities than other health measures. However, partly because of the present imperfections of such measures, drugs are needed and methods of reducing their end cost and increasing their effectiveness are important, particularly for the poor rural patient. The field is acutely influenced by social, ethical and political forces but there are direct technical questions which those most in need are not in a position to answer. These have to do with the extent to which drug compounding can be decentralized and the availability of equipment and of manuals on simple handling techniques.

Developing Countries↗
PubMed1992

Liquid preparations for oral administration.

Liquids are easier to swallow and act more quickly than solid dosage forms, but may be unpalatable and relatively unstable. Solutions contain dissolved drugs and may be difficult to formulate or to make palatable; suspensions are usually more pleasant to take but accuracy of dosing may be affected by settling of drug particles. The dose of a drug in liquid and solid form may differ because different drug compounds are often used. Liquids contain many additives which can give rise to adverse affects in the patient.

Chemistry, Pharmaceutical↗
PubMed1982

[Parameters of the liquid-liquid extraction of toxicologically relevant organic compounds. Part 1: Methodology of the experimental determination of partition constants and pH-dependent partition quotients; results obtained with acidic compounds].

Though liquid-liquid extraction is most widely used technique for isolating organic compounds (drugs, poisons), its fundamental parameters (partition constants and dissociation constants) are not determined explicitly in most cases; they are mostly estimated indirectly together with other factors in the form of resultants (total yield, detection sensitivities). For this reason we determined the partition quotients and their pH-dependence for more than 300 slightly volatile organic compounds (mainly drugs) in two-phase systems (aqueous buffer solution/solvent non-miscible with water). Nearly all the determinations were performed using diethyl ether and chloroform; other organic solvents were applied especially in studying slightly extractable compounds. The results obtained with 63 acidic compounds are reported.

Acids↗
PubMed1981

Genetic screening of compounds used in drug abuse treatment. II. Methadone.

Several compounds used clinically in drug abuse therapy were evaluated for genetic activity in a series of in vivo and in vitro assays. The second report in this series describes the results for one of these compounds, Methadone. A previous report described the results for Naltrexone. Methadone is a synthetic narcotic analgesic used as a substitute for Heroin in drug detoxification programs. Methadone demonstrated weak activity in the E. coli DNa repair system and in the Neurospora crassa and the mouse lymphoma forward-mutation assays under the conditions of this evaluation. Additional analysis of the ad-3 mutants induced by a related compound, LAAM, in Neurospora indicated that they were the result of a parasexual phenomena rather than forward mutation. Therefore, the methadone-induced ad-3 mutants also may be due to a parasexual phenomena.

Animals↗
PubMed1989

Asthma pharmacology: industrial/clinical interface.

The disease of asthma remains poorly understood. Hence, considerable latitude has been afforded to pharmacologists concerned to identify novel compounds for development as anti-asthma drugs. Compounds can be selected (1) on the basis of known efficacy as bronchodilator (beta-adrenoceptor agonists, parasympatholytics and xanthines) and prophylactic (cromoglycate and ketotifen) or anti-inflammatory (glucocorticosteroids) actions; (2) by reference to current theories of asthma pathogenesis, e.g., inhibition of the formation and action of autoacoids (leukotrienes, platelet-activating factor) or cytokines (GM-CSF, IL-5), or (3) by reference to hitherto unexplored physiological processes (K+ channel activation, PDE isoenzyme inhibition, selective immunosuppressive actions). There is a need to test whether the rationale for drug selection is justified. This can only be resolved by study of asthma patients, since normal subjects may respond inappropriately. Thus, normal subjects do not exhibit airway obstruction or airway hyperreactivity and hence do not respond to bronchodilator substances. Similarly, normal subjects respond to platelet-activating factor with a cellular infiltrate in which neutrophils predominate in contrast to atopic asthmatics who exhibit an eosinophilia. It follows that compound discovery and evaluation must be an iterative procedure in which animal studies are supplemented by clinical studies and vice versa. This is most readily achieved by establishing clinical research that is a complementary to preclinical research.

Asthma↗
PubMedDate not supplied

Bioidentical hormone therapy: a review.

OBJECTIVE: The terms "natural" or "bioidentical" hormone therapy (NHT) are used to describe hormone treatment with individually compounded recipes of certain steroids in various dosage forms, including dehydroepiandrosterone, pregnenolone, testosterone, progesterone, estrone, estradiol, and estriol. Based on the results of a person's salivary hormone levels, the final composition of the compounded dosage form is individualized to that specific person. Proponents claim that NHT is better tolerated than manufactured products. This paper is intended to review the concept of NHT and to determine whether there is sufficient scientific evidence to support its use. DESIGN: A literature search was performed in Medline using the following MeSH terms and key words: drug combinations; progestational hormones; hormone replacement therapy; endometrium; estrogen replacement therapy; climacteric; menopause; estradiol; estrogens; progesterone; drug monitoring; and drug compounding. Current Contents, International Pharmaceutical Abstracts, Cochrane Database of Systematic Reviews, Lexis Nexis, Google, Medscape, MD Consult, and clinicaltrials.gov were searched with key words. RESULTS: There are a few observational studies and clinical trials comparing conventional hormone therapy with bioidentical hormone therapy. Studies generally lacked adequate study design, including small sample sizes and comparison of inequivalent doses, to prove safety and efficacy. Little evidence was found to support individualized hormone dosing based upon saliva hormone concentrations. CONCLUSION: Evidence suggests that, although individualized hormonal products may decrease some symptoms of menopause, it seems they have no proven advantage over conventional hormone therapies and their use is not supported by evidence regarding pharmacokinetics, safety, and efficacy.

Drug Compounding↗
PubMed2003

Synthesis and evaluation of PEG414, a novel formulating agent that avoids analytical problems associated with polydisperse vehicles such as PEG400.

Polyethylene glycol (PEG) 400 is widely used as a formulating agent for both intravenous and oral studies during drug discovery. It is a polydisperse material containing more than 16 oligomers, which can cause significant problems for high-performance liquid chromatography-mass spectrometry analysis due to ion suppression and isobaric interference. To overcome these difficulties, we have synthesized the single oligomer PEG414. The material has been characterized with a range of diverse drug compounds and shown to be comparable to PEG400 and superior to propylene glycol in terms of its solubilization power. The toxicological and metabolic properties of PEG414 should be similar to PEG400. It suffers none of the analytical problems associated with polydisperse agents and we expect it to be a useful alternative for the formulation of test compounds for intravenous and oral dosing during drug discovery.

Chemistry, Pharmaceutical↗
PubMed1981

Genetic screening of compounds used in drug abuse treatment. III. LAAM.

Several compounds used clinically in drug abuse therapy were evaluated for genetic activity in a series of in vivo and in vitro assays. This third report in the series describes the results for one of these compounds, LAAM (L-alpha-acetyl methadol). Previous reports described results from a three phase testing program for Naltrexone and Methadone. LAAM is related chemically to the narcotic analgesic oxymorphine, and is related chemically to a narcotic antagonist, naloxone. LAAM exhibited genetic activity in the ad-3 forward-mutation test in Neurospora crassa and also was weakly mutagenic in the mouse lymphoma forward-mutation assay. Further analysis of the ad-3 mutants from N. crassa indicated that they were the result of a parasexual phenomenon rather than forward mutation. There was one confirmed translocation carrier in the heritable translocation study, which by conservative interpretation might imply some germ-cell risk associated with exposure to LAAM.

Animals↗
PubMed1995

Technical considerations in the preparation and dispensing of chemotherapy.

The safe handling of cytotoxic agents is intimately related to the technical aspects of drug preparation, dispensing, and administration. The appropriate equipment, supplies, protective clothing, and waste disposal systems must be available to the health care worker who is called upon to prepare cytotoxic agents. In addition, the health care worker must be adequately trained in and familiar with the safe use of these products and equipment and the preparation techniques or manipulations necessary during cytotoxic drug compounding. The article describes in detail and reviews the technical considerations, such as aseptic technique, proper use of the biological safety cabinet, gowning and gloving, labeling, and waste disposal, that are essential to the safe preparation and dispensing of chemotherapy.

Air Microbiology↗
PubMed2006

Generating monodisperse pharmacological aerosols using the spinning-top aerosol generator.

Pharmacological aerosols of precisely controlled particle size and narrow dispersity can be generated using the spinning-top aerosol generator (STAG). The ability of the STAG to generate monodisperse aerosols from solutions of raw drug compounds makes it a valuable research instrument. In this paper, the versatility of this instrument has been further demonstrated by aerosolizing a range of commercially available nebulized pulmonary therapy preparations. Nebules of Flixotide (fluticasone propionate), Pulmicort (budesonide), Combivent (salbutamol sulphate and ipratropium bromide), Bricanyl (terbutaline sulphate), Atrovent(ipratropium bromide), and Salamol (salbutamol sulphate) were each mixed with ethanol and delivered to the STAG. Monodisperse drug aerosol distributions were generated with MMADs of 0.95-6.7 microm. To achieve larger particle sizes from the nebulizer drug suspensions, the STAG formed compound particle agglomerates derived from the smaller insoluble drug particles. These compound agglomerates behaved aerodynamically as a single particle, and this was verified using an aerodynamic particle sizer and an Andersen Cascade Impactor. Scanning electron microscope images demonstrated their physical structure. On the other hand using the nebulizer drug solutions, spherical particles proportional to the original droplet diameter were generated. The aerosols generated by the STAG can allow investigators to study the scientific principles of inhaled drug deposition and lung physiology for a range of therapeutic agents.

Administration, Inhalation↗
PubMed2001

Fabrication of PLG microspheres with precisely controlled and monodisperse size distributions.

The size distribution of biodegradable polymer microspheres critically impacts the allowable routes of administration, biodistribution, and release rate of encapsulated compounds. We have developed a method for producing microspheres of precisely controlled and/or monodisperse size distributions. Our apparatus comprises spraying a polymer-containing solution through a nozzle with (i) acoustic excitation to produce uniform droplets, and (ii) an annular, non-solvent carrier stream allowing further control of the droplet size. We used this apparatus to fabricate poly(D,L-lactide-co-glycolide) (PLG) spheres. The acoustic excitation method, by itself, produced uniform microspheres as small as 30 microm in diameter in which > or =95% of the spheres were within 1.0-1.5 microm of the average. The carrier stream method alone allowed production of spheres as small as approximately 1-2 microm in diameter from a 100-microm diameter nozzle, but generated broader size distributions. By combining the two devices, we fabricated very uniform spheres with average diameters from approximately 5 to >500 microm. Furthermore, by discretely or continuously varying the experimental parameters, we fabricated microsphere populations with predefined size distributions. Finally, we demonstrate encapsulation and in vitro release of a model drug compound, rhodamine B. In summary, our apparatus provides unprecedented control of microsphere size and may allow development of advanced controlled-release delivery systems.

Algorithms↗