Pharmacokinetic-pharmacodynamic modelling of magnesium plasma concentration and blood pressure in preeclamptic women.
OBJECTIVE
To describe the relationship between plasma magnesium (Mg(2+)) concentration and blood pressure response in pregnant women with preeclampsia.


METHODS
Fifty-one preeclamptic women were studied after receiving two consecutive magnesium sulfate infusions (120 mg/kg for 1 hour and 24 mg/kg for 5 hours). Mg(2+) concentration and systolic/diastolic blood pressure were measured at 0, 0.5, 1, 2, 4, 6, 7, 9, 11, 13 and 15 hours after the beginning of the first infusion. A population pharmacokinetic-pharmacodynamic model was fitted to the data with the computer program NONMEM.


RESULTS
Pharmacokinetics were described by a two-compartment model. Population parameter estimates were 5.0 L/h for body clearance (CL), 24L for central volume (V(c), 25L for peripheral volume ((V)(p)) and 5.6 L/h for intercompartment clearance (Q). The interindividual variability in CL, V(c), V(p) and Q was 39, 26, 38, and 59%, respectively. The mean population estimates for systolic (diastolic) blood pressure were 36.8 (27.8) mm Hg for the maximum decrease (E(max)), 0.75 (0.88) mmol/L for the Mg2+ concentration (above baseline) eliciting half-maximum effect (EC(50)) and 0.76 (0.5) h(-1) for the equilibrium rate (k(eo)) of the effect compartment model.


CONCLUSIONS
Mg(2+ )concentrations within the range (2-4 mmol/L) proposed for treatment of preeclampsia produce greater than half-maximal lowering of systolic and diastolic blood pressure.
Lu
Jianfeng
J
Department of Biopharmaceutical Sciences, University of California San Francisco, 94143, USA.
Pfister
Marc
M
Ferrari
Paolo
P
Chen
Gang
G
Sheiner
Lewis
L
D001499:Bayes Theorem; D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008274:Magnesium / Q000097:blood*; D008278:Magnesium Sulfate / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D008954:Models, Biological; D015233:Models, Statistical; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000503:physiopathology; D011247:Pregnancy; D013997:Time Factors; D015149:Tocolytic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology
D015149:Tocolytic Agents; D008278:Magnesium Sulfate; D008274:Magnesium