Imaging of Cyclosporine Inhibition of P-Glycoprotein Activity Using ¹¹C-Verapamil in the Brain: Studies of Healthy Humans

(A) Verapamil in blood declined rapidly to an average of 37% on average at 45 min after injection. In this subject example, exponential washout function (—) fit to verapamil measurements (•) provided fraction of verapamil as a function of time. Metabolites of verapamil in plasma, D617 fraction (▴) and other, polar metabolites (▪) continually rose during imaging study, reaching a combined total metabolite fraction of over 60%. (B) Verapamil model input function, C_p-Ver, is a combination of total blood activity, C_B, and the fraction of verapamil determined from plasma metabolite analysis. Similar curves were obtained for all 12 subjects. Mean verapamil fraction at 45 min was 40% (range, 66%−24%), D617 fraction was 30% (range, 49%−17%), and other metabolites were 30% (range, 44%−16%).