Pharmacokinetics gastrointestinal tract disease

Absorption of theophylline from the gastrointestinal tract is usually rapid and complete. Some 90% is metabolised by the liver and there is evidence that the process is saturable at therapeutic doses. The tis 8 h, with substantial variation, and it is prolonged in patients with severe cardiopulmonary disease and cirrhosis. Obesity and prematurity are associated with reduced rates of elimination, whereas tobacco smoking enhances theophylline clearance by inducing hepatic P450 enzymes. Because of these pharmacokinetic factors and low therapeutic index, monitoring of the plasma theophylline concentration is necessary to optimise its therapeutic effect and minimise the risk of adverse reactions the optimum concentration range is 10-20 mg/1 (55-110 mmol/1). 

The absolute bioavailability of only a few drug compounds is affected by ESKD. An increase in bioavailability as the result of a decrease in metabolism during the drug s firstpass through the gastrointestinal tract and liver has been noted for some /3-blockers (i.e., bufu-ralol, oxprenolol, propranolol, and tolamolol), dextropropoxyphene, and dihydrocodeine. Although the bioavailability of these compounds is increased, clinical consequences (development of excessive or unexpected adverse effects) have only been demonstrated with dextropropoxyphene and dihydrocodeine. The lack of association between the pharmacokinetic profile and clinical consequences of the /3-blockers may result from an alteration in the responsiveness of patients with renal disease to these agents, as has been reported with propranolol in the elderly. ... 

Studies evaluating the potential for plant secondary metabolites to alter disease risk through effects on relevant cells and tissues other than those associated with the oral cavity and the gastrointestinal tract should assess the impact of the known metabolites present in vivo rather than the chemical forms that exist only in foods. Furthermore, the pharmacokinetic characteristics of the metabolites should be taken into consideration and efforts made to establish their biological activities at relevant physiologic concentrations. 

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