Pharmacokinetic-Pharmacodynamic Modelling of Magnesium Plasma Concentration and Blood Pressure in Preeclamptic Women
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- Lu, J., Pfister, M., Ferrari, P. et al. Clin Pharmacokinet (2002) 41: 1105. doi:10.2165/00003088-200241130-00007
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To describe the relationship between plasma magnesium (Mg2+) concentration and blood pressure response in pregnant women with preeclampsia.
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). Mg2+ 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.
Pharmacokinetics were described by a two-compartment model. Population parameter estimates were 5.0 L/h for body clearance (CL), 24L for central volume (Vc), 25L for peripheral volume (Vp) and 5.6 L/h for intercompartment clearance (Q). The interindividual variability in CL, Vc, Vp 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 (Emax), 0.75 (0.88) mmol/L for the Mg2+ concentration (above baseline) eliciting half-maximum effect (EC50) and 0.76 (0.5) h-1 for the equilibrium rate (keo) of the effect compartment model.
Mg2+ 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.