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  • Journal of Pharmaceutical Sciences
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  • 1
    Language: English
    In: Journal of Pharmaceutical Sciences, May 1974, Vol.63(5), pp.784-786
    Description: Investigations with ibuprofen [(±)-p-isobutylhydratropic acid], a well-tolerated, orally active, anti-inflammatory drug, were undertaken to: (a) determine the relationship among plasma drug concentrations, administered dose, and anti-inflammatory activity in developing and established polyarthritis in rats; and (b) compare the plasma drug disappearance half-lives in normal and polyarthritic rats. The results indicated that plasma drug concentrations in normal and polyarthritic rats were dose related. The logarithm of biological activity expressed as [% IPA/(100 – % IPA)], where % IPA is the mean percent inhibition of developing or established polyarthritis as measured by plasma inflammation units, was related to the logarithms of: (a) administered dose (mg kg−1), (b) plasma drug concentrations (μg ml−1) at 2hr postadministration, and (c) average plasma drug concentrations (μg ml−1) in a dosage interval at the equilibrium state. Half-lives for elimination of ibuprofen from the plasma of normal rats (after single-dose oral drug administration) and polyarthritic rats (after 29 doses) were essentially identical.
    Keywords: Ibuprofen—Plasma Levels Correlated With Biological Activity ; Biological Activity—Correlated With Ibuprofen Plasma Levels ; Anti-Inflammatory Agents—Ibuprofen Plasma Levels Correlated With Biological Activity ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0022-3549
    E-ISSN: 1520-6017
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  • 2
    Language: English
    In: Journal of Pharmaceutical Sciences, February 1974, Vol.63(2), pp.219-221
    Description: To evaluate the pharmacokinetics and drug availability from various dosage formulations, a method for the determination of ibuprofen [(±)-2-(p-isobutylphenyl)propionic acid] in human plasma was required. A simple, rapid, sensitive, and specific procedure, based on a benzene extraction of the acidified specimen and subsequent GLC analysis of the methyl esters of the extract residue, was developed. The method is sensitive to 0.5 μg ibuprofen/ml plasma. Statistical analyses indicate an average recovery of 94.8 ±6.6% (SD), which is adequate to differentiate assay error from normal biological variation. Mass spectrometric analysis, in conjunction with GLC, confirmed the specificity of the method for intact drug. The procedure was successfully applied to drug absorption studies in humans.
    Keywords: Ibuprofen—Glc Analysis in Human Plasma ; (±)- 2-(P-Isobutylphenyl)Propionic Acid (Ibuprofen)—Glc Analysis in Human Plasma ; Glc—Analysis, Ibuprofen in Human Plasma ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0022-3549
    E-ISSN: 1520-6017
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  • 3
    Language: English
    In: Journal of Pharmaceutical Sciences, May 1978, Vol.67(5), pp.627-630
    Description: To evaluate drug‐protein binding, a sensitive method for the determination of ibuprofen in submilliliter amounts of serum was required. A specific and highly sensitive procedure, based on benzene extraction of the acidified specimen, TLC of the benzene extract residue, formation of the pentafluorobenzyl esters of the materials eluted from the thin‐layer chromatogram, and quantification of the pentafluorobenzyl esters by GLC, was developed. Utilizing electron‐capture detection, the method is sensitive to 0.1 μg of ibuprofen/0.1 ml of serum. Statistical analyses indicated an average recovery of 97.7% with a standard deviation of ±7.3%. Mass spectrometric analysis, in conjunction with GLC, confirmed the specificity of the method for the intact drug. The procedure was applied successfully to drug absorption and drug‐protein binding studies in humans.
    Keywords: Ibuprofen—Electron-Capture Glc Analysis in Serum, Time Course of Protein Binding in Humans ; Glc, Electron Capture—Analysis, Ibuprofen in Serum ; Protein Binding—Ibuprofen in Humans, Time Course Studied Using Electron-Capture Glc Analysis in Serum ; Anti-Inflammatory Agents—Ibuprofen, Electron-Capture Glc Analysis in Serum, Time Course of Protein Binding in Humans ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0022-3549
    E-ISSN: 1520-6017
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  • 4
    Language: English
    In: Journal of Pharmaceutical Sciences, May 1975, Vol.64(5), pp.798-801
    Description: To study the behavior of the d- and l-isomers of ibuprofen in humans, a method for the determination of the individual enantiomers in plasma and urine was required. A specific procedure was developed based on (a) benzene extraction of the acidified specimens, (b) TLC of the benzene extract residue, (c) formation of the l-alpha-methylbenzylamides of the materials eluted from the chromatograms, and (d) quantification of the resulting diastereoisomeric amides by GLC in conjunction with flame-ionization detection. When using a 1-ml aliquot of the specimen, the method is sensitive to 1 mug of each enantiomer/ml of plasma or urine. As compared to simple aqueous solutions, the average recoveries of the enantiomers from plasma and urine ranged from 94 to96%. Mass spectrometric analyses, in conjunction with GLC, confirmed the specificity of the method for the intact enantiomers. The procedure was applied successfully to drug absorption studies in humans. After oral administration of the racemic mixture, the predominant enantiomer in peripheral circulation and excreted in urine was of the d-configuration.
    Keywords: Ibuprofen—Glc Determination of Enantiomers in Biological Specimens ; Glc-Determination, Ibuprofen Enantiomers in Biological Specimens ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0022-3549
    E-ISSN: 1520-6017
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  • 5
    Language: English
    In: Journal of Pharmaceutical Sciences, October 1974, Vol.63(10), pp.1579-1581
    Description: To evaluate the pharmacokinetics and potential drug interactions at relatively low doses (i.e., 7.5 mg), a method for the determination of warfarin in human plasma was required. A sensitive and specific procedure was developed based on: (a) ethylene chloride extraction of the acidified specimen, (b) TLC of the ethylene chloride extract residue, (c) formation of the pentafluorobenzyl derivatives of the materials eluted from the thin-layer chromatogram, and (d) quantification of the pentafluorobenzyl derivatives by GLC, utilizing electron-capture detection. The lower level of assay detection sensitivity for measurement of intact warfarin in plasma is 0.02 μg/ml. Statistical analyses indicate a recovery of 98.8%, with a standard deviation of ±10.9%. IR and mass spectrometric analyses, in conjunction with GLC, confirmed that the intact drug was being measured and that no interferences from blank plasma were observed. The procedure was successfully applied to drug absorption studies in humans.
    Keywords: Warfarin—Glc Determination in Human Plasma ; Anticoagulants—Glc Determination of Warfarin in Human Plasma ; Glc—Analysis, Warfarin in Human Plasma ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0022-3549
    E-ISSN: 1520-6017
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  • 6
    Language: English
    In: Journal of Pharmaceutical Sciences, 1972, Vol.61(12), pp.1908-1911
    Description: Investigations with 4,5-bis( -methoxyphenyl)-2-phenylpyrrole-3-acetonitrile, a potent anti-inflammatory, antiarthritic, and antipyretic drug, were undertaken to: ( ) develop a simple, rapid, sensitive, and specific method of analysis for the intact drug in biological matrixes; ( ) determine the relationship between plasma drug concentrations, administered dose, and anti-inflammatory activity in polyarthritic rats; ( ) compare the normalized plasma or serum drug concentrations in rats, dogs, and man when an equivalent oral dose was administered; and ( ) estimate the plasma or serum drug disappearance half-life in rats, dogs, and man after single-dose oral drug administration. The results indicated that plasma drug concentrations in the polyarthritic rat, as measured by fluorometric techniques, were dose related. Biological activity, expressed as mean percentage inhibition of arthritis, was related to the logarithm of the average plasma drug concentration (micrograms per milliliter) in a dosage interval at the equilibrium state. After single-dose oral drug administration, at calculated equivalent dose levels (milligrams per kilogram), drug concentrations found in the plasma or serum of human subjects were greater than those found in rats or dogs. The plasma drug disappearance half-life found in man ( ½ = 1.5-2.0 hr.) was more similar to dogs ( ½ = 1.5-2.0 hr.) than to rats ( ½ = 11.4 hr.).
    Keywords: 4,5-Bis(P-Methoxyphenyl)-2-Phenylpyrrole-3-Acetonitrile—Correlation of Plasma Levels With Biological Activity ; Plasma Levels, 4,5-Bis(P-Methoxyphenyl)-2-Phenylpyrrole-3-Acetonitrile—Correlated With Biological Activity ; Spectrophoto-Fluorometry—Analysis, 4,5-Bis (P-Methoxyphenyl)-2-Phenylpyrrole-3-Acetonitrile in Plasma ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0022-3549
    E-ISSN: 1520-6017
    Source: ScienceDirect Journals (Elsevier)
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  • 7
    Language: English
    In: Journal of Pharmaceutical Sciences, December 1975, Vol.64(12), pp.2011-2013
    Description: Interest in 2,3-bis(p-methoxyphenyl)imidazo[1,2-a]-pyrimidine as a potent, orally active, anti-inflammatory agent required a method for its determination in serum, urine, and feces to permit studies of its absorption, metabolism, and excretion. A simple, rapid, sensitive, and specific procedure was developed based on an ethyl acetate extraction of alkaline specimens and subsequent fluorometric analysis of ethanolic solutions of the extract residues. The method is sensitive to 0.2 mug/ml, 0.3 mug/ml, and 1.2 mug/100 mg of drug in serum, urine, and feces, respectively. The overall mean recovery and the standard deviation from biological samples are 99.8 +/- 5.1%. The procedure has been successfully applied to absorption studies in the dog.
    Keywords: 2,3‐Bis(P‐Methoxyphenyl)Imidazo[1,2‐a]Pyrimidine—Fluorometric Analysis, Biological Materials, Anti‐Inflammatory Agent ; Anti‐Inflammatory Agents—2,3‐Bis(P‐Methoxyphenyl)‐Imidazo[1,2‐a]Pyrimidine, Fluorometric Analysis, Biological Materials ; Fluorometry—Analysis, 2,3‐Bis(P‐Methoxyphenyl)Imidazo‐[1,2‐a]Pyrimidine, Anti‐Inflammatory Agent, Biological Materials ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0022-3549
    E-ISSN: 1520-6017
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  • 8
    Language: English
    In: Journal of Pharmaceutical Sciences, April 1974, Vol.63(4), pp.567-570
    Description: To evaluate the pharmacokinetics and drug availability from various dosage formulations, a method for the determination of dl-2-(2-fluoro-4-biphenylyl)propionic acid (flurbiprofen) in human plasma was required. A sensitive and specific procedure, based on (a) benzene extraction of the acidified specimen, (b) TLC of the benzene extract residue, (c) formation of the pentafluorobenzyl esters of the materials eluted from the thin-layer chromatogram, and (d) quantification of the pentafluorobenzyl esters by GLC, utilizing electron-capture detection, was developed. The lower level of assay detection sensitivity for measurement of flurbiprofen in plasma is 0.05 μg/ml. Statistical analyses indicated an average recovery of 97.1% with a standard deviation of ±9.2%. IR and mass spectrometric analyses, in conjunction with GLC, confirmed the specificity of the method for the intact drug. The procedure was successfully applied to drug absorption studies in humans.
    Keywords: Dl-2-(2-Fluoro-4-Biphenylyl)Propionic Acid (Flurbiprofen)—Glc Analysis in Plasma ; Flurbiprofen [Dl-2-(2-Fluoro-4-Biphenylyl)Propionic Acid]—Glc Analysis in Plasma ; Glc—Analysis, Flurbiprofen in Plasma ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0022-3549
    E-ISSN: 1520-6017
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  • 9
    Language: English
    In: Journal of Pharmaceutical Sciences, December 1976, Vol.65(12), pp.1767-1769
    Description: Interest in the 5-, 6-, and 7-trifluoromethyl-substituted 2,3-bis(4-methoxyphenyl)indoles as potent, orally active anti-inflammatory agents required a method for their determination in serum, urine, and feces to permit studies of their absorption, metabolism, and excretion. A simple, rapid, sensitive, and specific procedure was developed based on an ethyl acetate extraction of alkaline specimens and subsequent fluorometric analysis of ethanolic solutions of the extract residues. The method is sensitive to 0.1 microgram/ml, 0.5 microgram/ml, and 0.7 microgram/100 mg of these compounds in serum, urine, and feces, respectively. Overall mean recoveries and standard deviations of the 5-, 6-, and 7-trifluoromethyl-substituted compounds from biological samples were 102.2 +/- 3.0, 102.2 +/- 5.4, and 100.5 +/- 5.7%, respectively. The procedure was applied successfully to absorption studies with 2,3-bis(4-methoxyphenyl)-7-(trifluoromethyl)indole in the dog.
    Keywords: 2, 3-Bis(4-Methoxyphenyl)Indoles, Trifluoromethyl Substituted—Fluorometric Analysis, Serum, Urine, and Feces ; Fluorometry—Analysis, Trifluoromethyl-Substituted 2, 3-Bis(4-Methoxyphenyl)Indoles in Serum, Urine, and Feces ; Anti-Inflammatory Agents—Trifluoromethyl-Substituted 2, 3-Bis(4-Methoxyphenyl)-Indoles, Fluorometric Analysis in Serum, Urine, and Feces ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0022-3549
    E-ISSN: 1520-6017
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  • 10
    Language: English
    In: Journal of Pharmaceutical Sciences, November 1976, Vol.65(11), pp.1710-1710
    Keywords: Ibuprofen—Glc Analysis in Plasma, Effect of Varying Solid Support Materials ; Glc—Analysis, Ibuprofen in Plasma, Effect of Varying Solid Support Materials ; Solid Supports, Glc—Effect on Ibuprofen Analysis ; Anti‐Inflammatory Agents—Ibuprofen, Glc Analysis in Plasma, Effect of Varying Solid Support Materials ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0022-3549
    E-ISSN: 1520-6017
    Source: ScienceDirect Journals (Elsevier)
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