[Cyclosporin A and ketoconazole, drug interaction or therapeutical combination?]

Cyclosporin A is potentiated by ketoconazole, mainly by inhibiting its P-450 dependent biotransformations. The other interest of ketoconazole is related to its antifungal effect, which is often used in immunodepressed patients. Thus for both pharmacodynamic and pharmacokinetic reasons, the combination of the two drugs is of interest. Another advantage is that whereas ketoconazole is a cheap drug, cyclosporin A is an expensive one, thus their combination may save a part of the cyclosporin A cost. Various questions remain to be solved: is it useful to combine in the same tablet selected amounts of the two drugs and if so in which ratio? Such a strategy supposes that intra and inter-individual variability of cyclosporin A metabolism in humans can be tightly monitored. Is it without risk to definitely inhibit some P-450 isoenzymes? Could not the expected simplification of drug dosages generate the need for more cyclosporin A blood level assays, thus leading to an additional cost?