Isoenzyme system

Drug interactions Coadministration of cisapride, pimozide, dofetilide, orquinidine with itraconazole is contraindicated. Itraconazole is a potent inhibitor of the cytochrome P450 3A4 isoenzyme system and may raise plasma concentrations of... 

All SSRIs (e.g., Feonard et ah, 1997) and in particular fluoxetine, Fluvosamine and paroxetine are metabolized by hepatic cytochrome P450 enzymes. Therefore, it is important to be aware of the possibility that the therapeutic or toxic effects of other medications metabolized by the cytochrome P450 isoenzyme system can be increased. Substantial inhibition of these isoenzymes converts a normal metabolizer into a slow metabolizer with regard to this specific pathway. Inhibition of the hepatic oxidative isoenzymes has been associated with a reduction, to a varying extent, in the clearance of many therapeutic agents, including the TCAs, several neuroleptics, antiarrhythmics, theophy-lene, terfenadine, benzodiazepines, carbamazepine, and warfarin (for a complete list, see Nemeroff et ak, 1996). 

The second part of this project will investigate the applicability of the isoenzyme systems Glutathione Reductase and Peptidase A to dried blood analysis. The grantee proposes, also, to incorporate the Gm and Inv allotypes into routine use. Techniques for identifying these genetic markers are well-established for whole blood but must be adapted for dried blood analysis. Persistence studies will be undertaken to determine the viability of these different systems upon drying, to determine the effect of aging, to document the effect of various substrates, and to devise a practical system to type the isoenzymes and allotypes in dried blood. 

The choice and application of various methods of isoenzyme analysis in clinical enzymology are discussed in Chapter 21 in relation to specific isoenzyme systems. 

The modest improvements achieved in selectivity with respect to serotonin reuptake inhibition may also have been achieved with an isoenzyme system. Moclobemide, which was introduced in Sweden, reversibly inhibits monoamine oxidase A (RIMA). It is likely that this eliminates the severe hypertensive drug and food interactions that so severely limit the usefulness of the very effective earlier MAO inhibitors, since tyramine is now metabolized. An additional benefit of such agents may be a lack of cholinergic and cardiovascular effects. 

Of the newer antiepilepties, both felbamate and topiramate are weak inducers of CYP3A4. They may also inhibit CYP2C19. They are also partially metabolised by the cytochrome P450 isoenzyme system, so may have their metabolism altered by other drugs such as the older enzyme-inducing antiepileptics. 

The NNRTis are extensively metabolised by the cytochrome P450 isoenzyme system, particularly by CYP3A4. They are also inducers (nevirapine, efavirenz) or inhibitors (delavirdine) of CYP3A4. NNRTis would therefore be expected to interact with each other, and with protease inhibitors, but not with NRTIs (see below). They also have the potential to interact with other drugs metabolised by CYP3A4, and are affected by CYP3A4 inhibitors and inducers. Delavirdine and efavirenz may also inhibit some other P450 isoenzymes. For a summary, see Table 21.2 , (p.773). 

Danazol is a known inhibitor of the cytochrome P450 isoenzyme system.Ciclosporin is predominantly metabolised by the cytochrome P450 isoenzyme CYP3A4. It therefore seems likely that danazol raises ciclosporin levels by inhibiting its metabolism. 

Nicotinic acid has little effect on the cytochrome P450 isoenzyme system and is therefore unlikely to result in significant pharmacokinetic interactions. It also appears to increase the risk of myopathies when given with statins, see Statins + Nicotinic acid (Niacin) , p.ll06. Also note that al-... 

In barley both PGK isoenzymes are synthesized in total darkness. The synthesis of chloroplast PGK being promoted by light, especially when light is supplied at an early stage of leaf development. The increased synthesis seems to be controlled by Pfr. The synthesis of the cytosolic PGK may be inhibited by light or its breakdown promoted by light. Thus it is clear that a number of factors govern the content of the two isoenzymes of PGK in leaf tissue. It would also appear that a number of isoenzyme systems may prove useful in the early detection of senescence. 

Isoenzyme system Numbers of phenotype Methods of electrophoresis... 

Drug interactions since fentanyl is metabolized mainly via the human cytochrome P450 3A4 isoenzyme system (CYP3A4) possible interactions may occur when fentanyl buccal tablet or fentanyl oralet is given along with medications that affect CYP3A4 activity. 

Fentanyl is metabolized primarily in the liver via the cytochrome P450 3A4 isoenzyme system. It is metabolized primarily by JV-dealkylation to norfen-tanyl and other inactive metabolites that do not contribute materially to the observed activity of the drug. 

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