[Knowledge about metabolic capacity is important in drug therapy].
Genetic polymorphisms are common and are also found for drug metabolising enzymes such as acetyltransferase and two distinct cytochrome P-450 isoenzymes that catalyse the oxidative metabolism of the model drugs debrisoquine and S-mephenytoin respectively. Thus, individual metabolic activity can be categorised as slow or rapid. The metabolism of a number of drugs has been shown to cosegregate with that of either of these substrates. In subjects with slow metabolism of a certain drug, its effects might be enhanced due to increased concentrations either of the drug itself or of its active metabolite(s). In practice, knowledge of a patient's debrisoquine metabolic phenotype is an advantage when prescribing tricyclic antidepressants and neuroleptics, as the drug concentration will be considerably higher in slow metabolisers than in the average patient. Codeine has no analgesic effect in slow metabolisers of debrisoquine, probably due to deficient metabolism to morphine. Pharmacogenetic data can also be utilised as an aid in interpreting the drug concentrations obtained in therapeutic drug monitoring programmes. The metabolism of diazepam, omeprazol, and proguanil is associated with the capacity to oxidise S-mephenytoin. Proguanil requires metabolic activation before it has any effect on the malaria parasite and this reaction seems severely impaired in slow metabolisers of S-mephenytoin. So far, no unequivocal relationship has been established as existing between drug oxidation phenotypes and spontaneous disease manifestations. The potential clinical importance of polymorphic metabolic drug elimination needs to be taken into consideration in assessing drugs.
Alván
G
G
Aydelningen för klinisk farmakologi, Huddinge sjukhus.
Dahl
M L
ML
D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003647:Debrisoquin / Q000378:metabolism; D006801:Humans; D008617:Mephenytoin / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010641:Phenotype; D011110:Polymorphism, Genetic
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D008617:Mephenytoin; D003647:Debrisoquin
Viktigt känna till metabolisk kapacitet vid läkemedelsbehandling.