Population pharmacokinetics of ketanserin in pre-eclamptic patients and its association with antihypertensive response.
Ketanserin is an antihypertensive drug that is increasingly being used parenterally in the treatment of pre-eclampsia. Because of lack of efficacy in a substantial part of our pre-eclamptic patients, we determined the plasma concentrations of ketanserin in 51 pre-eclamptic patients. Population pharmacokinetic parameters were assessed using the iterative two-stage Bayesian population procedure. The influence of individual pharmacokinetic parameters on antihypertensive response, expressed as the attainment of a diastolic blood pressure <or=90 mmHg using ketanserin treatment, was analysed. Almost all plasma concentrations of ketanserin were in or above the therapeutic range. The individual pharmacokinetics of ketanserin in pre-eclamptic patients showed an accurate fit using a three-compartment model. The pharmacokinetic parameters in our pre-eclamptic population were a metabolic clearance (Cl(m)) of 37.9+/-10.86 L/h and volume of distribution (V1) of 0.544+/- 0.188 L/kg, which is comparable with data from healthy volunteers. Despite a considerable inter-individual variation, no correlation was found between differences in pharmacokinetic parameters and antihypertensive response. We conclude that therapeutic plasma levels can be obtained in pre-eclamptic patients with a fixed dosage schedule of ketanserin and differences in antihypertensive responses within a pre-eclamptic population cannot be attributed to pharmacokinetic differences.
Hanff
Lidwien M
LM
Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. l.hanff@erasmusc.nl
Visser
Wil
W
Steegers
Erik A P
EA
Vulto
Arnold G
AG
D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007262:Infusions, Intravenous; D007650:Ketanserin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D011225:Pre-Eclampsia / Q000188:drug therapy* / Q000503:physiopathology; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D013997:Time Factors; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D007650:Ketanserin