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This thesis argues that ancient Greek narratives of encounter between gods and mortals cannot be understood simply in terms of constellations of recurrent descriptive features or in terms of the iterability of type-scene or ritual. Divine epiphanies are moments of disruption or antistructure which provoke strategic, structuring responses, not least in narrative and ritual. But these responses do not subsume the potential that remains at the intersection between gods and mortals. Contestation over power, authority and legitimacy is constitutive of epiphany. In the first section I examine problems caused by scholarly concern for 'authentic experience' in treating epiphany-accounts in general and Homeric epic in particular. I propose an alternative focus on how sense, both as perception and as significance, is actively produced in such contexts: narrativisation and ritualisation offer experiences-in-themselves in which people participate to make sense and significance in the world. The cultural currency of such narratives depends not on their relation to religious experiences or religious belief as such, but on the ways that such narratives engage their audiences in exploring the difference of gods from mortals and the ramifications of this difference for human existence in the world. In the second section I consider a succession of moments in the Iliad and the Odyssey, first to destabilise the notion of divine epiphany as a self-evident category or paradigm, second to explore the vital importance of three questions: what constitutes divine presence and absence, how they are manifested, and how they might or might not be recognised. The expression of divine presence in figurative terms in Homer does not reflect a metaphorisation of divine power, but is constitutive of the problematic play of divine presence and mortal recognition. The consequences of recognising or failing to recognise this play of presence and absence can be profound. Even when contemplating the 'body' of the gods, problems of perception and point-of-view are operative. Viewing divine epiphany as an interplay of presence and perception points to the importance of the specific constituting frames of presence and absence. Contestation and realisation of authority and legitimacy are crucial concomitants. I explore the ends of the Odyssey and Iliad in terms of the authority of gods to end our narratives and the potential for mortals to generate specifically human meanings in and around these ends. In my conclusion I look beyond Homer briefly to consider the ongoing place of narratives of divine epiphany in Greek cultural contexts. How significance is generated in relation to the presence and absence of the gods remains a central question, and the disruptive tropes of epiphany play a crucial role.

There are many benefits of predicting pharmacokinetic properties before administration to man. Recently it has become apparent that the in vivo clearance of drugs from in vitro metabolic data can be predicted with some degree of accuracy. To substantiate and extend this approach, a database of metabolic in vitro and in vivo data in rat was established for a total of 35 drugs. The database was then utilised to validate in vitro intrinsic clearance (CLint) scaling factors (1200M hepatocytes/SRW and 660mg microsomal protein/SRW). Poorly predicted drugs were then identified by applying discrimination criteria for predictive success of 50% under prediction to 100% over prediction. Of those, ethoxycoumarin (EC) and phenacetin (PNC) were chosen for closer examination with their in vivo and in vitro estimates of CLint being determined using the isolated perfused liver preparation (IPL), freshly isolated hepatocytes and hepatic microsomes. The CLints obtained for both EC and PNC from the IPL experiments under predicted the observed CLints but gave reproducible results and demonstrated the ability to reflect the trends of increasing CLint with decreasing dose and induction with beta-Naphthoflavone (betaNF). The IPL system used in the experiments was a simple one in terms of the perfusate. There were no blood cells or protein added nor was monitoring of oxygen and pH carried out. Therefore, if the IPL was to be used as a substitute for an in vivo study to determine hepatic clearance it may be necessary to use a more sophisticated system. EC depletion data from hepatocytes gave a good 84% prediction of in vivo CLint with microsomes giving a poor 38% prediction, due possibly, to end product inhibition. However, on induction with BNF, hepatocytes and microsomes both gave good predictions of 130 and 70% respectively. It was suggested that induction with BNF induces CYP isoforms which are less susceptible to end product inhibition. Predictions based upon 7-hydroxycoumarin formation data were consistent with those carried out previously and expectedly under predicted CLint. This is consistent with the existence of other pathways of metabolism. These studies demonstrated the utility of drug depletion data to predict in vivo CLint when the complete metabolic fate of a drug is unknown. The metabolism of PNC was monitored via the formation of paracetamol. When compared to the in vivo CLint, corrected for the fraction metabolised to paracetamol, hepatocytes gave a prediction of 50% with microsomes giving a prediction of 31%. End product inhibition was investigated and was shown not to be a factor in the microsomal prediction. However, recently published studies demonstrated that paracetamol could be produced from routes other than via direct O-deethylation of PNC. A further correction was made to the in vivo CLint to take into account the role of futile deacetylation which then allowed an acceptable microsomal prediction of 50% to be made. The predictions of EC and PNC CLint arising from the work carried out in this thesis were an improvement on those previously obtained by other workers. If the 50% under prediction to 100% over prediction acceptance criteria are applied, only the microsomal prediction of EC CLint would be considered as an unacceptable prediction. Use of the drug depletion approach, as demonstrated with EC, may become the method of choice to predict in vivo clearance as it overcomes metabolite identification and separation difficulties often encountered during drug metabolism studies.