Effects of two calcium antagonists on hemodynamics and on cyclosporine pharmacokinetics were studied in eight transplant patients (four heart-transplant and four kidney-transplant patients) by use of a single-blind, randomized, crossover, and placebo-controlled design. Patients received, at least 1 week apart, either 90 mg diltiazem, 20 mg nifedipine (in tablet form), or placebo, given 1 hour before cyclosporine. Cyclosporine and its main metabolite (metabolite 17) were measured in plasma (separated at 25 degrees C) by use of HPLC. Both calcium antagonists tended to increase absorption rate and elimination rate, but none of the pharmacokinetic parameters of cyclosporine were significantly altered. Moreover, the area under the curve of plasma concentrations of metabolite 17 did not change. On the other hand, both nifedipine and diltiazem significantly altered the hemodynamics, but to a different extent in the two groups of patients. The heart-transplant patients showed larger decreases in systolic and diastolic blood pressure than the kidney-transplant patients after administration of both nifedipine and diltiazem, but they showed smaller increases in cardiac index and heart rate with nifedipine. In contrast, diltiazem caused small decreases in heart rate and cardiac index in heart-transplant patients and small increases in heart rate and cardiac index in kidney-transplant patients. We conclude that a single dose of either nifedipine or diltiazem does not affect, to a clinically significant extent, the pharmacokinetics of cyclosporine. In addition, heart-transplant patients show different hemodynamic responses to these two calcium antagonists than the responses shown by kidney-transplant patients, probably because of cardiac denervation.

Ten healthy male volunteers were given 200 mg p.o. of isoxicam after an overnight fast and the plasma concentrations over time followed for 96 h by h.p.l.c. Five days later enteric coated acetylsalicylic acid (ASA) 650 mg four times daily was started and continued for 10 days producing steady state trough plasma salicylate of 83 mg/l (range 21‐133). A second 200 mg isoxicam dose was given 5 days after starting ASA and the plasma concentration time‐curve again followed. After ASA, there was no change in lag time (0.54 vs 0.51 h), time to peak concentration (10 vs 10 h), or disappearance t1/2 (28.7 vs 31.0 h) however the peak isoxicam concentration and AUC were reduced 18 and 22% respectively (P less than 0.01). Plasma protein binding of isoxicam studied by equilibrium dialysis was 96 +/‐ 1% in the absence and 86 +/‐ 5% in the presence of ASA. The reduction in binding was unrelated to plasma SA concentrations achieved or observed reductions in AUC for plasma isoxicam. ASA decreased plasma isoxicam binding, peak plasma isoxicam concentrations and AUC without altering the apparent disappearance half‐life of total plasma isoxicam after a single oral dose.