Changes in Antipyrine and Indocyanine Green Kinetics During Nifedipine, Verapamil, and Diltiazem Therapy

Ten healthy subjects received oral antipyrine and intravenous indocyanine green (ICG) alone and after 5 days of oral nifedipine, diltiazem, and verapamil. Antipyrine clearance decreased during verapamil (range 4% to 26%) and diltiazem (6% to 24%) therapy (P less than 0.001) but did not change during nifedipine treatment. Antipyrine t1/2 also increased during verapamil and diltiazem treatment (P less than 0.001). ICG clearance did not change during diltiazem therapy but increased during dosing with nifedipine and verapamil (P less than 0.05). Estimated liver blood flow (derived from ICG clearance and hematocrit) also increased during verapamil (mean 33%) and nifedipine (mean 27%) treatment (P less than 0.05). Drug interactions with other liver-metabolized drugs may occur during therapy with these calcium antagonists. Nifedipine appears to increase liver blood flow whereas diltiazem inhibits oxidative drug metabolism. Drug interactions with verapamil could involve both mechanisms.