Clinical Pharmacokinetics

, Volume 41, Issue 13, pp 1105–1113

Pharmacokinetic-Pharmacodynamic Modelling of Magnesium Plasma Concentration and Blood Pressure in Preeclamptic Women

  • Jianfeng Lu
  • Marc Pfister
  • Paolo Ferrari
  • Gang Chen
  • Lewis Sheiner
Original Research Article

DOI: 10.2165/00003088-200241130-00007

Cite this article as:
Lu, J., Pfister, M., Ferrari, P. et al. Clin Pharmacokinet (2002) 41: 1105. doi:10.2165/00003088-200241130-00007

Abstract

Objective

To describe the relationship between plasma magnesium (Mg2+) 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). 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.

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 (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.

Conclusion

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.

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  • Jianfeng Lu
    • 1
    • 2
  • Marc Pfister
    • 1
    • 3
  • Paolo Ferrari
    • 3
  • Gang Chen
    • 2
  • Lewis Sheiner
    • 1
  1. 1.Department of Biopharmaceutical SciencesUniversity of California San FranciscoSan FranciscoUSA
  2. 2.Jinling HospitalChina
  3. 3.Division of Nephrology/HypertensionUniversity of BerneBerneSwitzerland
  4. 4.NON-MEM Group, C255University of California at San FranciscoSan FranciscoUSA

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