The influence of infusion rate on the pharmacokinetics and haemodynamic effects of nisoldipine in man

Publication Type:

Journal Article

Authors:

van Harten, J.; van Brummelen, P.; Zeegers, R.R.; Danhof, M.; Breimer, D.D.

Source:

Br J Clin Pharmacol, Volume 25, Number 6, p.709-17 (1988)

ISBN:

0306-5251 (Print)

Keywords:

Adsorption; Adult; Female; Hemodynamics/*drug effects; Humans; Indocyanine Green/diagnostic use; Infusions; Intravenous; Liver Circulation/drug effects; Male; Nifedipine/administration; &; dosage/*analogs; &; derivatives/pharmacokinetics/pharmacology;

Abstract:

1. The pharmacokinetics and haemodynamic effects of nisoldipine on long term i.v. infusion of 2.40 mg and 9.59 mg in 25 h were studied in six healthy subjects. Liver blood flow at 0.8 and 24 h was assessed by measuring indocyanine green (ICG) clearance. 2. After high-dose nisoldipine, systemic clearance was 0.99 +/- 0.16 1 min-1, volume of distribution was 5.8 +/- 1.5 1 kg-1 and elimination half-life was 10.7 +/- 2.4 h. The pharmacokinetic parameters were similar after low-dose nisoldipine. 3. No significant changes in apparent liver blood flow were observed after either high-dose or low-dose nisoldipine. 4. Systolic blood pressure did not change, whereas diastolic blood pressure decreased by approximately 10% during both treatments. Maximal increase in heart rate was approximately 37% at high-dose infusion, whereas this was one half lower during the low-dose regimen. 5. Increased infusion rate results in an unfavourable shift in the haemodynamic effect profile of nisoldipine.