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Interactions of FK506 with the cyclosporin A (CsA) metabolism are described. These interactions were not differentiated between the primary and secondary part of metabolism. The combination-therapy with cyclosporin A and diltiazem has shown, that not only the blood levels of CsA were increased, but also the blood levels of the primary CsA-metabolite M17. In the presented in in-vitro-investigations 1.7 microM tritium-labelled CsA was incubated for 90 min with human liver microsomes. The inhibitory effect of FK506 (6 microM) was observed with coincubation under the same conditions. The metabolites were quantified by detection of radioactivity of the elution-fractions after HPLC. The results showed strong inhibition on the formation of both, the primary and secondary CsA-metabolites by FK506. With the same concentration diltiazem and erythromycin exhibited only an inhibition of the formation of secondary CsA-metabolites. In clinical investigations with FK506 in combination with CsA it is necessary to control blood levels of CsA and also its primary metabolites.
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