The study of the metabolism of phenylbutazone (4-butyl-1,2 -diphenylpyrazolidine - 3,5 - dione) in rats
- Authors: Alexander, Dorothy Mary
- Date: 1978 , 2013-10-18
- Subjects: Drugs -- Metabolism , Phenylbutazone
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3832 , http://hdl.handle.net/10962/d1007468 , Drugs -- Metabolism , Phenylbutazone
- Description: In this study the metabolism of the anti-arthritic drug, phenylbutazone, was investigated in female Wistar rats, and the results compared with those of other workers in this field. Two interrelated projects were undertaken. The first covered the pattern of excretion, isolation and characterisation of the metabolites and decomposition products of phenylbutazone in rats dosed post-orally with the drug. It was found that the major route of excretion was via the urine and over 50% of the administered dose was excreted in the first 24 hours by this route. A small percentage of the dose was excreted in the faeces. The following compounds were identified using chromatographic and autoradiographic techniques: p-Hydroxy derivative of phenylbutazone γ-Hydroxy derivative of phenylbutazone in both its molecular forms (ring lactone and straight chain hydroxyl) 4-Hydroxy derivative of phenylbutazone p-γ-Dihydroxy derivative of phenylbutazone p-4-Dihydroxy derivative of phenylbutazone Hydrolysable conjugates (possibly glucuronides) Water soluble non-hydrolysable conjugates. The second project dealt with the quantitation of the water insoluble compounds isolated in the initial work. Using a unique technique, combining inverse isotope dilution assay and spectrophotometric analysis, it was found that the major metabolite was the γ-hydroxy derivative of phenylbutazone, present in both its molecular forms. Oxyphenbutazone was a minor metabolite and the p-γ-dihydroxy derivative of phenylbutazone was present only in very low concentration. These results did not conform with those of previous workers in this field who reported the γ-hydroxy derivative of phenylbutazone, in one molecular form only, as the major metabolite and the dihydroxy derivative as the second metabolite with a higher concentration in the urine than oxyphenbutazone. This disparity could be due to the fact that these workers took no account of the presence of the two molecular forms of the γ-hydroxy derivative of phenylbutazone with their different polarities and different Rf values. The present study showed that the straight chain hydroxyl isomer was probably mistakenly identified as the p-γ-dihydroxy derivative of phenylbutazone. This theory is supported by the fact that the percentage dose recovered by the previous workers of the γ-hydroxy and p-γ-dihydroxy derivatives together equalled the percentage dose recovered in this study of the two molecular forms of the γ-hydroxy derivative. , KMBT_363 , Adobe Acrobat 9.54 Paper Capture Plug-in
- Full Text:
- Date Issued: 1978
- Authors: Alexander, Dorothy Mary
- Date: 1978 , 2013-10-18
- Subjects: Drugs -- Metabolism , Phenylbutazone
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3832 , http://hdl.handle.net/10962/d1007468 , Drugs -- Metabolism , Phenylbutazone
- Description: In this study the metabolism of the anti-arthritic drug, phenylbutazone, was investigated in female Wistar rats, and the results compared with those of other workers in this field. Two interrelated projects were undertaken. The first covered the pattern of excretion, isolation and characterisation of the metabolites and decomposition products of phenylbutazone in rats dosed post-orally with the drug. It was found that the major route of excretion was via the urine and over 50% of the administered dose was excreted in the first 24 hours by this route. A small percentage of the dose was excreted in the faeces. The following compounds were identified using chromatographic and autoradiographic techniques: p-Hydroxy derivative of phenylbutazone γ-Hydroxy derivative of phenylbutazone in both its molecular forms (ring lactone and straight chain hydroxyl) 4-Hydroxy derivative of phenylbutazone p-γ-Dihydroxy derivative of phenylbutazone p-4-Dihydroxy derivative of phenylbutazone Hydrolysable conjugates (possibly glucuronides) Water soluble non-hydrolysable conjugates. The second project dealt with the quantitation of the water insoluble compounds isolated in the initial work. Using a unique technique, combining inverse isotope dilution assay and spectrophotometric analysis, it was found that the major metabolite was the γ-hydroxy derivative of phenylbutazone, present in both its molecular forms. Oxyphenbutazone was a minor metabolite and the p-γ-dihydroxy derivative of phenylbutazone was present only in very low concentration. These results did not conform with those of previous workers in this field who reported the γ-hydroxy derivative of phenylbutazone, in one molecular form only, as the major metabolite and the dihydroxy derivative as the second metabolite with a higher concentration in the urine than oxyphenbutazone. This disparity could be due to the fact that these workers took no account of the presence of the two molecular forms of the γ-hydroxy derivative of phenylbutazone with their different polarities and different Rf values. The present study showed that the straight chain hydroxyl isomer was probably mistakenly identified as the p-γ-dihydroxy derivative of phenylbutazone. This theory is supported by the fact that the percentage dose recovered by the previous workers of the γ-hydroxy and p-γ-dihydroxy derivatives together equalled the percentage dose recovered in this study of the two molecular forms of the γ-hydroxy derivative. , KMBT_363 , Adobe Acrobat 9.54 Paper Capture Plug-in
- Full Text:
- Date Issued: 1978
A study of the rabbit eye test system to determine the activity of acidic non-steroidal anti-inflammatory agents
- Authors: Wiseman, Ian Charles
- Date: 1977
- Subjects: Nonsteroidal anti-inflammatory agents , Anti-inflammatory agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3855 , http://hdl.handle.net/10962/d1013276
- Description: From introduction : "Inflammation per se, has been defined sufficiently to permit a rational approach to the search for drugs that modify this process, but satisfactory animal models for most rheumatoid diseases are not available". (Swingle 1974) In the search for new meaningful procedures for the detection and evaluation of anti-inflammatory drugs, the rabbit eye as a test system was studied.
- Full Text:
- Date Issued: 1977
- Authors: Wiseman, Ian Charles
- Date: 1977
- Subjects: Nonsteroidal anti-inflammatory agents , Anti-inflammatory agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3855 , http://hdl.handle.net/10962/d1013276
- Description: From introduction : "Inflammation per se, has been defined sufficiently to permit a rational approach to the search for drugs that modify this process, but satisfactory animal models for most rheumatoid diseases are not available". (Swingle 1974) In the search for new meaningful procedures for the detection and evaluation of anti-inflammatory drugs, the rabbit eye as a test system was studied.
- Full Text:
- Date Issued: 1977
A gas chromatographic study of oils from some Agathosma species (family Rutaceae)
- Persicaner, Peter Henry Robert
- Authors: Persicaner, Peter Henry Robert
- Date: 1972 , 2013-11-13
- Subjects: Rutaceae , Rutaceae -- Therapeutic use , Gas chromatography
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3837 , http://hdl.handle.net/10962/d1007634 , Rutaceae , Rutaceae -- Therapeutic use , Gas chromatography
- Description: From Introduction: Buchu leaf is a very widely used household medicine in South Africa, and is usually administered in the form of a brandy tincture or a vinegar, known as "buchu brandy" and "buchu vinegar" respectively. These preparations have a great reputation in curing diseases of the kidney and urinary tract, and in addition are employed as local applications to bruises, and for the relief of rheumatic pains. We owe its introduction into medicine to the Hottentot, who gave the name "buchu" or "bookoo" to any aromatic herb or shrub which they found suitable for use as a dusting powder.
- Full Text:
- Date Issued: 1972
- Authors: Persicaner, Peter Henry Robert
- Date: 1972 , 2013-11-13
- Subjects: Rutaceae , Rutaceae -- Therapeutic use , Gas chromatography
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3837 , http://hdl.handle.net/10962/d1007634 , Rutaceae , Rutaceae -- Therapeutic use , Gas chromatography
- Description: From Introduction: Buchu leaf is a very widely used household medicine in South Africa, and is usually administered in the form of a brandy tincture or a vinegar, known as "buchu brandy" and "buchu vinegar" respectively. These preparations have a great reputation in curing diseases of the kidney and urinary tract, and in addition are employed as local applications to bruises, and for the relief of rheumatic pains. We owe its introduction into medicine to the Hottentot, who gave the name "buchu" or "bookoo" to any aromatic herb or shrub which they found suitable for use as a dusting powder.
- Full Text:
- Date Issued: 1972
An investigation into chemical and biological assays of new compounds from aloes
- Authors: Mapp, R K
- Date: 1969
- Subjects: Medicinal plants -- Research -- South Africa , Botanical chemistry , Aloe -- Analysis , Aloe -- Research -- South Africa , Aloe , Aloin
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3850 , http://hdl.handle.net/10962/d1012830
- Description: The drug aloes has been known since earliest times and is mentioned in the Ebers papyrus of circa 1,500 B.C. Alexander the Great is reported to have sent a commission to Socotra to investigate the aloes grown there. The chemical composition of aloes is complex, and being of plant origin, subject to variation. Both the complexity of the chemical constituents and their biological variation has resulted in a very large volume of conflicting material being published on this drug export. Since aloes is used as a purgative for both human and veterinary use, it is obviously important that the dosage and consequently the active constituents, should comply to an accurate means of standardisation. To date, despite extensive world wide research into this drug such standardisation has not been achieved. Even the methods used for the assay of the principal constituent, aloin, vary considerably in their results, and to complicate matters new chemical principles have been isolated from aloes in recent years. Consequently the purpose of this work has been to investigate the main chemical assay methods currently in use, and to determine which was the most accurate, and why discrepancies occurred in the selected assay methods. furthermore the results obtained by chemical assay have been compared with those obtained by biological assay in an attempt to correlate aloin content with purgative activity. Newly isolated compounds have been investigated biologically for the first time, and the biological assays of the resinous, glycosidal and other compounds of aloes have been performed. Intro. p.1-2.
- Full Text:
- Date Issued: 1969
- Authors: Mapp, R K
- Date: 1969
- Subjects: Medicinal plants -- Research -- South Africa , Botanical chemistry , Aloe -- Analysis , Aloe -- Research -- South Africa , Aloe , Aloin
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3850 , http://hdl.handle.net/10962/d1012830
- Description: The drug aloes has been known since earliest times and is mentioned in the Ebers papyrus of circa 1,500 B.C. Alexander the Great is reported to have sent a commission to Socotra to investigate the aloes grown there. The chemical composition of aloes is complex, and being of plant origin, subject to variation. Both the complexity of the chemical constituents and their biological variation has resulted in a very large volume of conflicting material being published on this drug export. Since aloes is used as a purgative for both human and veterinary use, it is obviously important that the dosage and consequently the active constituents, should comply to an accurate means of standardisation. To date, despite extensive world wide research into this drug such standardisation has not been achieved. Even the methods used for the assay of the principal constituent, aloin, vary considerably in their results, and to complicate matters new chemical principles have been isolated from aloes in recent years. Consequently the purpose of this work has been to investigate the main chemical assay methods currently in use, and to determine which was the most accurate, and why discrepancies occurred in the selected assay methods. furthermore the results obtained by chemical assay have been compared with those obtained by biological assay in an attempt to correlate aloin content with purgative activity. Newly isolated compounds have been investigated biologically for the first time, and the biological assays of the resinous, glycosidal and other compounds of aloes have been performed. Intro. p.1-2.
- Full Text:
- Date Issued: 1969
An investigation of chlorbutol in ophthalmic and parenteral solutions
- Authors: Summers, Robert Stanley
- Date: 1967
- Subjects: Parenteral solutions , Solutions (Pharmacy) , Ocular pharmacology
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3842 , http://hdl.handle.net/10962/d1007694 , Parenteral solutions , Solutions (Pharmacy) , Ocular pharmacology
- Description: From Introduction Chlorbutol , which is tri-chlor-tertiary-butanol, was first prepared by Willgerodt in 1886 (1). The reaction he used for its preparation is still used today, though slightly modified (2)(3)(4), and is suggested by its original name "acetone-chloroform". The substance was prepared by adding solid potassium hydroxide to a cold mixture of acetone and chloroform (5 ). Chlorbutol is a derivative of the trichlorinated derivative of methane, and its formation may best be described by the use of structural formulae.
- Full Text:
- Date Issued: 1967
- Authors: Summers, Robert Stanley
- Date: 1967
- Subjects: Parenteral solutions , Solutions (Pharmacy) , Ocular pharmacology
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3842 , http://hdl.handle.net/10962/d1007694 , Parenteral solutions , Solutions (Pharmacy) , Ocular pharmacology
- Description: From Introduction Chlorbutol , which is tri-chlor-tertiary-butanol, was first prepared by Willgerodt in 1886 (1). The reaction he used for its preparation is still used today, though slightly modified (2)(3)(4), and is suggested by its original name "acetone-chloroform". The substance was prepared by adding solid potassium hydroxide to a cold mixture of acetone and chloroform (5 ). Chlorbutol is a derivative of the trichlorinated derivative of methane, and its formation may best be described by the use of structural formulae.
- Full Text:
- Date Issued: 1967