Document Detail

Pharmacokinetic-pharmacodynamic modelling of magnesium plasma concentration and blood pressure in preeclamptic women.
MedLine Citation:
PMID:  12403646     Owner:  NLM     Status:  MEDLINE    
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. CONCLUSION: 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.
Jianfeng Lu; Marc Pfister; Paolo Ferrari; Gang Chen; Lewis Sheiner
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Clinical pharmacokinetics     Volume:  41     ISSN:  0312-5963     ISO Abbreviation:  Clin Pharmacokinet     Publication Date:  2002  
Date Detail:
Created Date:  2002-10-29     Completed Date:  2003-04-09     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7606849     Medline TA:  Clin Pharmacokinet     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  1105-13     Citation Subset:  IM    
Department of Biopharmaceutical Sciences, University of California San Francisco, 94143, USA.
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MeSH Terms
Bayes Theorem
Blood Pressure / drug effects*
Infusions, Intravenous
Magnesium / blood*
Magnesium Sulfate / administration & dosage,  pharmacokinetics*,  pharmacology
Models, Biological
Models, Statistical
Pre-Eclampsia / metabolism*,  physiopathology
Time Factors
Tocolytic Agents / administration & dosage,  pharmacokinetics*,  pharmacology
Grant Support
Reg. No./Substance:
0/Tocolytic Agents; 7439-95-4/Magnesium; 7487-88-9/Magnesium Sulfate

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