Fast metabolisers

In a preliminary report of a study in 7 non-smoking subjects who were fast metabolisers of propafenone, phenobarbital 100 mg daily for 3 weeks reduced the levels of a single 300-mg dose of propafenone by 26 to 87% and the AUC by 10 to 89%. The intrinsic clearance inereased by 11 to 84%. The results in a further 4 heavy smokers were similar. These ehanges probably occur because phenobarbital (a potent stimulator of liver enzymes) increases the metabolism of the propafenone. The elinical importance of this awaits assessment, but check that propafenone remains effective if phenobarbital is added, and that toxicity does not occur if it is stopped. If the suggested mechanism is correct, other barbiturates would be expected to interact similarly. 

The documentation is limited, but a clinieally important and potentially serious interaction is established between isoniazid and carbamazepine. Toxicity can develop quickly (within 1 to 5 days) and also seems to disappear quickly if the isoniazid is withdrawn. Concurrent use should not be undertaken unless the effects can be closely monitored and suitable downward dosage adjustments made (a reduction to between one-half or one-third was effective in 3 patients ). It seems probable that those who are slow metabolisers of isoniazid may show this interaction more quickly and to a greater extent than fast metabolisers. ... 

Rifampicin (a known potent liver enzyme inducer) increases the metabolism and clearance of the phenytoin from the body so that a larger dose is needed to maintain adequate serum levels. Isoniazid inhibits the liver microsomal enzymes that metabolise phenytoin, and as a result the phenytoin accumulates and its serum levels rise. Only those who are slow acetylators (slow metabolisers) of isoniazid normally attain blood levels of isoniazid that are sufficiently high to cause extensive inhibition of the phenytoin metabolism. Fast acetylators (fast metabolisers) remove the isoniazid too quickly for this to occur. Acetylator status is genetically determined. Thus some individuals will show a rapid rise in phenytoin levels, which eventually reaches toxic concentrations, whereas others will show only a relatively slow and unimportant rise to a plateau within, or only slightly above the therapeutic range. 

Metabolism via normal metabolic pathways or fast excretion without metabolism are desirable characteristics. Some intense sweeteners are excreted unchanged while others are metabolised. Bulk sweetener absorption is lower and slower than for carbohydrates and results in reduced caloric availability which is partly due to metabolites formed by intestinal bacteria. Such metabolites and osmotic effects of not fully absorbed bulk sweeteners can cause laxative effects. Generally, the calorific value of bulk sweeteners is lower than for carbohydrates. Intense and bulk sweeteners are, as far as they are metabolised, not dependent on insulin. They are therefore acceptable for diabetics as part of a suitable diet. 

Artemisinin is a natural endoperoxide-containing sesquiterpene, isolated from a plant used in traditional Chinese medicine. Acetalic artemisinin derivatives (arte-mether, artesunate) are very active against chemo-resistant forms of Plasmodium falciparum, and are clinically used for the treatment. However, they suffer from an unfavourable pharmacological profile. They are quickly metabolised by fast oxidative metabolism, hydrolytic cleavage and glucuronidation. 

Serum phenytoin levels are markedly reduced by rifampicin, but can be raised by isoniazid. Those who are slow acetylators (slow metabolisers) of isoniazid may develop phenytoin toxicity if the dosage of phenytoin is not reduced appropriately. If rifampicin and isoniazid are given together, serum phenytoin levels may fall in patients who are fast acetylators of isoniazid, but may occasionally rise in those who are slow acetylators. Clofazimine may reduce serum phenytoin levels. 

While fiver microsomes from male rats metabolise xenobiotics fast than fiver microsomes from female rats, enzyme preparations from rat lung (benzphe-tamine demethylase, p-chloro-W-methylanifine de-methylase, benzpyrene hydroxylase, UDP-glucuronyltransferase) and gut did not show sex differences in metabolism of several drug substrates (Chhabra and Pouts 1974). 

Poultry excrete faeces and urine together (but negligible methane). Apparent ME measurements (AME) can be corrected for endogenous losses (measured in fasted birds) to provide estimates of true metabolisable energy (TME). 

In addition to their energy losses in faeces, urine and methane, animals also lose energy as heat. Part of their heat loss arises from the work done by the animal in digesting and metabolising food (heat increment of feeding). The remainder, called the basal or fasting metabolism, arises from the work done by the animal associated with essential body processes (i.e. maintenance). 

A hen weighing 2.0 kg has a fasting metabolism of about 0.36 MJ/kg per day, or 0.60 MJ/day, and utUises metabolisable energy for maintenance and production with a combined efficiency of about 0.8. Its requirement for metabolisable energy... 

However, although it seems that Biomax sufficiently disintegrates under composting conditions [100], the final metabolisation of the material in a reasonable time scale is still under discussion. The producer itself admits that Biomax in the current formulation (June 2000) does not degrade fast enough to meet the accepted standards and thus, will improve the material with regard to its biodegradability [101]. 

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