The influence of infusion rate on the pharmacokinetics and haemodynamic effects of nisoldipine in man.
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.
van Harten
J
J
Center for Bio-Pharmaceutical Sciences, Division of Pharmacology, Leiden, The Netherlands.
van Brummelen
P
P
Zeegers
R R
RR
Danhof
M
M
Breimer
D D
DD
D000327:Adsorption; D000328:Adult; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007208:Indocyanine Green; D007262:Infusions, Intravenous; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D015737:Nisoldipine; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
D014665:Vasodilator Agents; D015737:Nisoldipine; D009543:Nifedipine; D007208:Indocyanine Green