Application of high-performance liquid chromatography to the analysis, stability and pharmacokinetics of erythromycin
- Authors: Stubbs, Christopher
- Date: 1988
- Subjects: Erythromycin High performance liquid chromatography
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3809 , http://hdl.handle.net/10962/d1004372
- Description: Erythromycin is a macrolide antibiotic used mainly in the treatment of infections caused by gram-positive organisms. Erythromycin base is rap idly degraded in acidic media necessitating the use of structurally modified erythromycin derivatives or acid resistant dosage forms in order to decrease gastric inactivation of the drug. The majority of pharmacokinetic studies to-date have utilized relatively non-specific microbiological assay procedures which are unable to differentiate between concentrations of active erythromycin base and the inactive pro-drug derivatives. A high-performance liquid chromatographic (HPLC) technique is described for the simultaneous determination of erythromycin base and propionate (inactive pro-drug form) in human serum and urine following the oral administration of erythromycin estolate, an acid stable derivative of erythromycin. The method involves a solid-phase extraction step prior to chromatography on a C18 reversed-phase column with coulometric electrochemical detection. Sample handling and storage techniques are presented which minimize hydrolysis of the inactive ester moiety between sample collection and analysis, thereby more accurately reflecting the in vivo situation than in previously published studies. Results from single dose pharmacokinetic studies indicate that only 10-15% of the total erythromycin concentration in vivo is present as the active base component following oral administration of erythromycin estolate. This percentage increases to approximately 25% during multiple dose administration. Novel urinary excretion data are presented which reveal that approximately 40% and 55% of the total erythromycin excreted in urine is excreted as erythromycin base following single and multiple dosages respectively. Computer fitting of mean serum concentration-time data revealed that an open one compartment model with linear first order absorption and elimination best described the absorption and disposition of erythromycin, although poor computer fits for individual data sets were observed. Some evidence of non-linear elimination is presented utilizing both compartmental and non-compartmental pharmacokinetic techniques. Large intra-and inter-personal variability in erythromycin absorption and disposition was experienced which was evaluated in five subjects who each received one 500 mg erythromycin estolate tablet from the same batch, on three separate occasions. In addition. an HPLC method is described for the analysis of "total erythromycin" concentrations following erythromycin estolate administration which involves hydrolysis of the ester component prior to chromatography. as well as an HPLC method utilizing amperometric electrochemical detection capable of monitoring the stability of erythromycin base in stored biological fluids. These methods were uti I ized in various stability studies involving erythromycin base and propionate as well as for the analysis of erythromycin estolate dosage forms.
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- Date Issued: 1988
Aspects of the biology and population dynamics of the geelbek Atractoscion aequidens (Cuvier) (Pisces: Sciaenidae) off the South African coast
- Authors: Griffiths, Marc H
- Date: 1988
- Subjects: Sciaenidae -- South Africa Fish populations -- South Africa Atractoscion Atractoscion -- South Africa -- Ecology Atractoscion -- South Africa -- Physiology
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5194 , http://hdl.handle.net/10962/d1001970
- Description: The geelbek Atractoscion aeguidens is an important commercial and recreational linefish species along the South African eastern seaboard . Aspects of its biology and population dynamics were investigated using data collected from various sampling sites along the South African east coast and from catch statistics obtained from both the Sea Fisheries Research Institute (Cape Town), and dealer records. The biological aspects studied included age and growth, reproduction and feeding. It was established that A. aeguidens is a fast growing species with a relatively late age at sexual maturity and a 1:1 sex ratio. Feeding studies revealed that it has become specialized to feed on small pelagic fish. The South African geelbek stock consists of three distinct age related sub-populations, each representing a particular phase in the life cycle. The sub-adults (1-4 yrs) occur in the South West Cape and feed predominantly on anchovy, Engraulis capensis, which they follow, moving inshore in summer and offshore in winter. The adults (5-9 yrs) undergo a seasonal inshore migration to Natal where they spawn in spring. The dynamics of this migration are strongly influenced by the annual movement of their principal prey viz. , Sardinops ocellatus, to that region. As a result the geelbek first arrive in Natal during mid winter. Evidence is also presented to suggest that a significant number of "adolescent " fish (4-5 yrs) undergo limited gonad maturation and a partial migration to at least as far as the South East Cape. Spawning appears to occur offshore. It is postulated that eggs and larvae are transported southwards by the peripheral waters of the Agulhas Current. After spawning the adults probably remain offshore and use the current to aid their return to the South and South West Cape, where they spend summer feeding on the Agulhas Bank. Juveniles (<1 yr) first appear in the South East Cape between January and March. They apparently use this region as a nursery area for almost a year before moving southwards to join the sub-adults in the South West Cape. In the South East Cape, the juveniles feed initially on mysids whereafter they switch to anchovies and pilchards. A preliminary stock assessment using yield per recruit and spawner biomass per recruit models, indicated that despite the current legislation the South African geelbek population is already overexploited. This is largely attributed to high rates of fishing mortality of the migratory adult population. Further management recommendations are therefore proposed. These include a size limit (660 mm FL), derived from an investigation of the interrelationship between natural mortality and somatic growth in a theoretical unexploited cohort, as well as a uniform bag limit for all user groups (5 fish per person per day)
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- Date Issued: 1988