High-performance liquid chromatographic studies of the acid degradation, pharmacokinetics and comparative bioavailability of erythromycin
- Authors: Glew, Fiona
- Date: 1989
- Subjects: High performance liquid chromatography , Erythromycin -- Analysis , Erythromycin -- Pharmacokinetics , Erythromycin -- Bioavailability
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3737 , http://hdl.handle.net/10962/d1001529
- Description: Erythromycin is a macrolide antibiotic with a spectrum similar to penicillin and is used mainly in the treatment of infections caused by gram-positive organisms. Since its discovery in 1952, erythromycin has achieved wide-spread clinical use. Susceptibility of erythromycin base to inactivation by acid results in decreased availability following exposure to acidic gastric fluids. Formulation of acid resistant dosage forms and the preparation of acid stable chemical derivatives have been attempted to improve absorption and subsequent clinical efficacy . Two of the most commonly used erythromycin derivatives are the stearic acid salt (erythromycin stearate) and the lauryl sulphate salt of the propionyl ester (erythromycin estolate). Although it has been known for many years that erythromycin is susceptible to acid degradation, very few reports on the stability of erythromycin in aqueous solutions appear in the literature. In this study, a high-performance liquid chromatographic system using electrochemical detection was employed for a kinetic study of erythromycin degradation. The effect of varying acid pH on the degradation rate of both erythromycin base and erythromycin stearate, and the effect on the hydrolysis rate of erythromycin estolate is presented. In addition, the effect of temperature on erythromycin degradation was also investigated. Until recently, the majority of pharmacokinetic and bioavailability studies have utilized relatively non-specific microbiological assay procedures. However, in this study a solid phase extraction, followed by the use of a high-performance liquid chromatographic system using electrochemical coulometric detection was employed for the determination of erythromycin in biological fluids. Human volunteers each received enteric coated erythromycin base pellets in capsule dosage form and also film coated erythromycin stearate tablets on separate occasions. Results from the clinical trials revealed the enteric coated erythromycin base pellets had a greater bioavailability than the film coated erythromycin stearate tablets. Computer fitting of data revealed no intra-volunteer variability in elimination rate constants, suggesting differences in serum levels following administration of both dosage forms are due to variation in absorption. Results from the clinical trials were also compared with those obtained from a further trial, during which the same volunteers received erythromycin estolate
- Full Text:
- Authors: Glew, Fiona
- Date: 1989
- Subjects: High performance liquid chromatography , Erythromycin -- Analysis , Erythromycin -- Pharmacokinetics , Erythromycin -- Bioavailability
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3737 , http://hdl.handle.net/10962/d1001529
- Description: Erythromycin is a macrolide antibiotic with a spectrum similar to penicillin and is used mainly in the treatment of infections caused by gram-positive organisms. Since its discovery in 1952, erythromycin has achieved wide-spread clinical use. Susceptibility of erythromycin base to inactivation by acid results in decreased availability following exposure to acidic gastric fluids. Formulation of acid resistant dosage forms and the preparation of acid stable chemical derivatives have been attempted to improve absorption and subsequent clinical efficacy . Two of the most commonly used erythromycin derivatives are the stearic acid salt (erythromycin stearate) and the lauryl sulphate salt of the propionyl ester (erythromycin estolate). Although it has been known for many years that erythromycin is susceptible to acid degradation, very few reports on the stability of erythromycin in aqueous solutions appear in the literature. In this study, a high-performance liquid chromatographic system using electrochemical detection was employed for a kinetic study of erythromycin degradation. The effect of varying acid pH on the degradation rate of both erythromycin base and erythromycin stearate, and the effect on the hydrolysis rate of erythromycin estolate is presented. In addition, the effect of temperature on erythromycin degradation was also investigated. Until recently, the majority of pharmacokinetic and bioavailability studies have utilized relatively non-specific microbiological assay procedures. However, in this study a solid phase extraction, followed by the use of a high-performance liquid chromatographic system using electrochemical coulometric detection was employed for the determination of erythromycin in biological fluids. Human volunteers each received enteric coated erythromycin base pellets in capsule dosage form and also film coated erythromycin stearate tablets on separate occasions. Results from the clinical trials revealed the enteric coated erythromycin base pellets had a greater bioavailability than the film coated erythromycin stearate tablets. Computer fitting of data revealed no intra-volunteer variability in elimination rate constants, suggesting differences in serum levels following administration of both dosage forms are due to variation in absorption. Results from the clinical trials were also compared with those obtained from a further trial, during which the same volunteers received erythromycin estolate
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Phenylpropanolamine : analytical and pharmacokinetic studies using high-performance liquid chromatography
- Authors: Scherzinger, Sabine Hilda
- Date: 1988
- Subjects: Phenylpropanolamine , Pharmacokinetics , High performance liquid chromatography
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: vital:3811 , http://hdl.handle.net/10962/d1004528
- Description: Phenylpropanolamine (PPA), a synthetic sympathomimetic amine structurally related to ephedrine has been widely used over t he past 40 years as a nasal decongestant and appetite suppressant. It has been the focus of much controversy concerning the efficacy of the drug in its use as an anorectic agent, and due to the side effects caused by the higher doses of PPA required for appetite suppression. Although extensively used, there is little information concerning the determination of PPA in biological fluids and on the pharmacokinetics of this drug. An adaptation of a published high-performance liquid chromatographic (HPLC) assay for PPA in serum and urine using U.V. detection at 210 nm is presented. PPA was separated in the reversed phase mode. The method has a limit of sensitivity of 5.0 ng/mL and 10.0 ng/mL in serum and urine respectively. Serum concentration data following a single 25 mg dose of phenylpropanolamine in human volunteers demonstrate the application of the analytical method for bioavailability and pharmacokinetic studies. After the administration of 25 mg, 50 mg or 100 mg PPA.HCl solutions to 5 human volunteers, a dose proportionality study demonstrated that PPA appears to exhibit linear kinetics. Linear one body compartment kinetics were assumed and the wagner-Nelson method used to transform in vivo serum data to absorption plots. The serum data were fitted to a model using nonlinear regression techniques to characterize the pharmacokinetic processes of PPA. The absorption of phenylpropanolamine appears to be discontinuous and the drug seems to favour a two body compartment model. The pharmacokinetic parameters obtained from a steady state study using multiple dosing of PPA.HCl solutions compared with those found from previous studies after the administration of sustained-release formulations. A plasma protein binding study using equilibrium dialysis demonstrated that PPA is not highly protein bound in the blood.
- Full Text:
- Authors: Scherzinger, Sabine Hilda
- Date: 1988
- Subjects: Phenylpropanolamine , Pharmacokinetics , High performance liquid chromatography
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: vital:3811 , http://hdl.handle.net/10962/d1004528
- Description: Phenylpropanolamine (PPA), a synthetic sympathomimetic amine structurally related to ephedrine has been widely used over t he past 40 years as a nasal decongestant and appetite suppressant. It has been the focus of much controversy concerning the efficacy of the drug in its use as an anorectic agent, and due to the side effects caused by the higher doses of PPA required for appetite suppression. Although extensively used, there is little information concerning the determination of PPA in biological fluids and on the pharmacokinetics of this drug. An adaptation of a published high-performance liquid chromatographic (HPLC) assay for PPA in serum and urine using U.V. detection at 210 nm is presented. PPA was separated in the reversed phase mode. The method has a limit of sensitivity of 5.0 ng/mL and 10.0 ng/mL in serum and urine respectively. Serum concentration data following a single 25 mg dose of phenylpropanolamine in human volunteers demonstrate the application of the analytical method for bioavailability and pharmacokinetic studies. After the administration of 25 mg, 50 mg or 100 mg PPA.HCl solutions to 5 human volunteers, a dose proportionality study demonstrated that PPA appears to exhibit linear kinetics. Linear one body compartment kinetics were assumed and the wagner-Nelson method used to transform in vivo serum data to absorption plots. The serum data were fitted to a model using nonlinear regression techniques to characterize the pharmacokinetic processes of PPA. The absorption of phenylpropanolamine appears to be discontinuous and the drug seems to favour a two body compartment model. The pharmacokinetic parameters obtained from a steady state study using multiple dosing of PPA.HCl solutions compared with those found from previous studies after the administration of sustained-release formulations. A plasma protein binding study using equilibrium dialysis demonstrated that PPA is not highly protein bound in the blood.
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Development of a high pressure liquid chromatographic method for the simultaneous analysis of sulphamethoxazole and trimethoprim and its application to biological fluids and dissolution rate studies on solid oral dosage forms
- Authors: Gochin, Rosa
- Date: 1980
- Subjects: High performance liquid chromatography , Body fluids -- Analysis , Drugs -- Dosage forms
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3735 , http://hdl.handle.net/10962/d1001524
- Description: Co-trimoxazole, a combination of a 5-to-l ratio of Sulphamethoxazole (SMZ) and Trimethoprim (TMP) , is a highly effective, broad-spectrum antibacterial agent. Since its introduction in 1968, it has been extensively used in infections of the respiratory and urinary tracts. Co-trimoxazole was developed by the systematic investigation of a series of compounds whose mechanism of action was already known. As early as 1950 synergy between sulphonamides and 2,4-diaminopyrimidines was reported. This was to be expected as both groups of drugs exert their antibacterial activity by interfering with the same biochemical pathway in bacteria. TMP was chosen from among many 2,4-diaminopyrimidines tested because of its good antibacterial activity and low toxicity. SMZ was chosen from the sulphonamides available for combination with TMP because of similarity of their biological half-lives. The widespread use of the combination coupled with the fact that monitoring of the levels of all drugs in the body is becoming increasingly important has stimulated research into rapid and efficient methods for the analysis of TMP and SMZ in biological fluids. Another consequence of the immense popularity of the combination is the appearance on the market of several generic preparations of Co-trimoxazole. It is now generally recognized that drug products from different manufacturers which are chemically equivalent may not be therapeutically equivalent. This is due to the fact that the absorption rate and/or bioavailability (extent of absorption) of a poorly soluble drug may be markedly affected by its release rate from the product and by its subsequent dissolution rate in gastrointestinal fluids. Hence bioequivalence of these various products should be established
- Full Text:
- Authors: Gochin, Rosa
- Date: 1980
- Subjects: High performance liquid chromatography , Body fluids -- Analysis , Drugs -- Dosage forms
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3735 , http://hdl.handle.net/10962/d1001524
- Description: Co-trimoxazole, a combination of a 5-to-l ratio of Sulphamethoxazole (SMZ) and Trimethoprim (TMP) , is a highly effective, broad-spectrum antibacterial agent. Since its introduction in 1968, it has been extensively used in infections of the respiratory and urinary tracts. Co-trimoxazole was developed by the systematic investigation of a series of compounds whose mechanism of action was already known. As early as 1950 synergy between sulphonamides and 2,4-diaminopyrimidines was reported. This was to be expected as both groups of drugs exert their antibacterial activity by interfering with the same biochemical pathway in bacteria. TMP was chosen from among many 2,4-diaminopyrimidines tested because of its good antibacterial activity and low toxicity. SMZ was chosen from the sulphonamides available for combination with TMP because of similarity of their biological half-lives. The widespread use of the combination coupled with the fact that monitoring of the levels of all drugs in the body is becoming increasingly important has stimulated research into rapid and efficient methods for the analysis of TMP and SMZ in biological fluids. Another consequence of the immense popularity of the combination is the appearance on the market of several generic preparations of Co-trimoxazole. It is now generally recognized that drug products from different manufacturers which are chemically equivalent may not be therapeutically equivalent. This is due to the fact that the absorption rate and/or bioavailability (extent of absorption) of a poorly soluble drug may be markedly affected by its release rate from the product and by its subsequent dissolution rate in gastrointestinal fluids. Hence bioequivalence of these various products should be established
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