Steady state pharmacokinetic haemodynamic studies of intravenous nitroglycerin in congestive cardiac failure

Abstract

We conducted pharmacokinetic haemodynamic studies in 10 patients with congestive cardiac failure to determine both the time to steady state concentration after commencement of a standard infusion rate of 21 micrograms/min i.v. GTN and the haemodynamic response once steady state plasma concentration ws achieved. Nitroglycerin was detected in plasma 2 min after commencement of the infusion, the concentration rose to a peak of approximately 4 ng/ml at 30 min and was maintained throughout the balance of the infusion period. During GTN infusion heart rate, systolic blood pressure and cardiac index were unchanged; there was significant declines (P less than 0.01) in pulmonary systolic pressure (SPA) (52 to 42 mm Hg), pulmonary capillary wedge pressure (PCWP) (26 to 20 mm Hg), and right atrial pressure (RAP) (12 to 8 mm Hg). These pressure changes were first evident within 5 min, approached maximum by 10 min and were maintained throughout the remainder of the infusion period. A one compartment model fitted to haemodynamic and GTN data revealed time constants (+/- approximate standard error) for SPA, PCWP, RAP and GTN of 8.2 (3.4), 9.7 (3.0), 8.1 (3.8) and 8.1 (1.9 respectively. Clearance for GTN was 6.2 +/- 2.7 (s.d.) 1 min. These data demonstrate steady state concentration of GTN is approached asymptotically with a time constant of 8.1 min during i.v. infusion of 21 micrograms/min. The time constants for haemodynamic measurement most sensitive to GTN's effect, i.e. SPA, PCW and RAP were remarkably similar to the time constant found for GTN concentration.(ABSTRACT TRUNCATED AT 250 WORDS)