CHARLES Bruce (1,2), CHUAN Francine (1), BOYLE Rhonda (3), RASIAH Rohan (4)
(1) School of Pharmacy, (2) Australian Centre for Paediatric Pharmacokinetics, University of Queensland, (3) Department of Anaesthetic Services, Royal Women's Hospital, (4) Pharmacy Services, Mater Misericordiae Hospitals, Brisbane, Qld, Australia
AIM: To determine the population pharmacokinetics (PK) of magnesium sulphate (Mg) in the perinatal period from sparse observational data in preeclamptic patients.
METHODS: An intravenous Mg load (16 mmol or 20 mmol) followed by a constant-rate infusion of 1 mmol/h over an average of 28 h was administered to 147 patients (mean age 27; range 17-43 years) from two Brisbane teaching hospitals. Serum Mg was assayed by dye-binding colorimetry (working range 0.05-4.1 mmol/L; CV% <3.5%). A one-compartment model was fitted to the data. Population estimates of Mg clearance (CL), volume of distribution (V) and baseline Mg concentration (B) were obtained by NONMEM (5.1.1) using FOCE with interaction. The interindividual variability of each PK parameter and the residual variability were estimated using exponential and additive error models, respectively. Endogenous Mg was assumed to be at steady-state with linear kinetics such that its contribution was modeled as an additive, incremental response to administered Mg.
RESULTS: There were 294 (pre-delivery 81, post-delivery 213) samples (mean 1.46, range 0.59-2.78 mmol/L), including 17 pre-dose samples (9 preeclamptics), and 31 samples from other monitored antenatal patients of whom 7 were preeclamptics who did not require Mg. The following typical values with interindividual variabilities (CV%) were obtained:- CL, 4.28 L/h (37.3%); V, 32.3 L (32.1%); B, 0.811 mmol/L (18.5%). The Mg elimination half-life (derived from the population typical values for CL and V) was 5.2 h. Clonus was not obtunded in 4 patients whose serum Mg concentrations were similar to the average value of 1.7 mmol/L. The unexplained variability was 6.5% (hospital #1), and 10.8% (hospital #2).
CONCLUSION: The results of this study are useful for the calculation of load and maintenance doses in preeclamptic patients, particularly when the relationship between effect(s) and serum Mg concentration become more clearly established from further clinical studies.
Reference: PAGE 10 (2001) Abstr 171 [www.page-meeting.org/?abstract=171]
Poster: poster