The effect of food on pharmacokinetics and pharmacodynamics of fenoldopam in class III heart failure.

Eighteen patients with New York Heart Association class III congestive heart failure were given single 100 mg oral doses of fenoldopam with food or fasting in a random-order single-blind crossover trial. Before and after each fenoldopam dose, thermodilution cardiac output, right atrial pressure, pulmonary artery pressure, and pulmonary capillary wedge pressure (PCWP) were measured with a balloon-tipped pulmonary artery catheter, and heart rates and blood pressures were recorded with an automated sphygmomanometer. Compared with fasting, bioavailability of fenoldopam was decreased significantly when administered with food: mean peak plasma fenoldopam level decreased from 26.5 (+/- 4.1 SEM) ng/ml to 10.9 (+/- 1.7 SEM) ng/ml (p = 0.0004) and mean area under the concentration-time curve was decreased from 44.7 (+/- 5.8 SEM) ng.hr/ml to 26.8 (+/- 4.1 SEM) ng.hr/ml (p = 0.0001). Fenoldopam administration to fasting patients resulted in decreases in mean arterial pressure, systemic vascular resistance, and PCWP and significant increases in cardiac index without change in heart rate. The maximum changes in mean cardiac index, systemic vascular resistance, and PCWP were greatest 1 hour after oral administration and did not persist beyond 3 hours after administration. In fasting patients, changes in cardiac index were correlated with plasma fenoldopam levels, whereas changes in PCWP and mean arterial pressure did not correlate significantly with the observed fenoldopam level.

Antihypertensive effect of tiapamil from ambulatory and clinic methods.

Tiapamil (T), a calcium antagonist, was studied in hypertensive patients by 1) automatic monitor of blood pressure (AMBP), and 2) cuff and stethoscope clinic blood pressure (CBP). Systolic (SBP), diastolic (DBP) pressures and heart rate were measured. Patients (n = 58) received four weeks of placebos given twice daily. Baseline 24 h AMBP (wk 4), 147 +/- 18 (SBP) and 91 +/- 8 (DBP) mmHg; and CBP (wk 3 and 4), 152 +/- 16 (SBP) and 102 +/- 9 (DBP) were established. Then, patients received double-blinded therapy (wk 5-10) of twice daily tablets of placebo (n = 9); Level I T, 150-300 mg (n = 24); or Level II T, 450-600 mg (n = 25): i.e. 0 to 1,200 mg T/d. Significant responses, measured by AMBP (wk 10), were noted only at Level II T: SBP (-10.5 +/- 12.4) and DBP (-5.6 +/- 7.8) mmHg. However, CBP (wk 9 and 10) responded at Level I T (SBP, -7.7 +/- 12.4/DBP, -5.8 +/- 6.4) and Level II T (SBP, -8.8 +/- 9.4/DBP, -9.7 +/- 7.8 mmHg). There was minimal correlation (r = 0.16) of pressure responses to T measured by 24-h AMBP versus CBP methods. Therefore, T effectively lowered SBP and DBP, but individual responses measured by AMBP did not predict those measured by CBP. There was no effect of T on heart rate. Dizziness was noted in 12 percent of patients on T.