Variability in the pharmacokinetics of nisoldipine as caused by differences in liver blood flow response.
We investigated whether the effect of nisoldipine on liver blood flow depends on its route of administration. Ten healthy subjects took nisoldipine I.V. (infusion) and orally (without and with sotalol pretreatment). Pharmacokinetics of nisoldipine was assessed and liver blood flow (ICG clearance) was measured before dosing and at the end of the infusion or during absorption. During I.V. infusion the ICG plasma clearance increased by only 14%, whereas the increase was 60% during absorption of nisoldipine. Nisoldipine increases liver blood flow considerably only during the absorption phase. A positive correlation was found between the increase in liver blood flow during absorption and the systemic availability of nisoldipine, suggesting that the differences in liver blood flow response to nisoldipine substantially contribute to the variability in pharmacokinetics of the drug.
Leiden University, Division of Pharmacology, The Netherlands.
J
J
van Harten
P
P
van Brummelen
P
P
Ooms
M
M
Danhof
G J
GJ
Blauw
D D
DD
Breimer
D000284:Administration, Oral; D000328:Adult; D001800:Blood Specimen Collection; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics* / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007208:Indocyanine Green; D007275:Injections, Intravenous; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D015737:Nisoldipine; D013015:Sotalol / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015737:Nisoldipine; D013015:Sotalol; D009543:Nifedipine; D007208:Indocyanine Green