E.M. Parker, M. Hutchison
Zeneca Pharmaceuticals
Introduction: Meropenem is a broad spectrum carbapenem antibiotic which is likely to be useful in children.
Aims: To estimate population pharmacokinetic parameters of Meropenem in children using NONMEM. To look at relationships between weight (wt), creatinine clearance (CLcr), age, sex, body surface area (BSA), race, infected/not infected and the pharmacokinetic parameters.
Method: Single dose data from 72 children who each received a 30 minute infusion of meropenem (10, 20 or 40 mg/kg) were analysed using NONMEM. Between 2 and 7 blood samples were collected between 0.5 and 8 hours following the beginning of infusion from each child. A biexponential pharmacokinetic model, parameters: volume in central compartment (V), volume at steady state (Vss), clearance from central compartment (CL) and distributional clearance (CLd), were used to describe the data.
Results: Both V and Vss were directly related to wt. CL was directly related to CLcr as expected for a predominantly renally excreted drug. Both CL and CLd were dependent on age in the younger children (mainly under 5 years of age).
| V(L)=0.21*wt*(l+ηv) | var(ηv)=0.14 | CV=38 % |
| Vss (L)=0.46*wt*(l+ηvss) | var(ηvss)=0.072 | CV=27 % |
| CL(L/hr) = 1.6*age/(0.58+age)*CLcr*(l+ηCL) | var(ηCL)=0.16 | CV=40 % |
| CLd(L/hr)=4.9*age/(0.57+age)*(l+ηCLd) | var(ηCLd)= 0.094 | CV=31 % |
| Cij (ug/L)=Cij+Cij0.39*ξ ij | var(ξ)=0.55 |
where Cij is the ith observed and Cij is ith predicted concentration for the jth individual.
Sex, BSA, race or infected/not infected did not appear to influence the pharmacokinetics of meropenem.
Summary: The pharmacokinetics of meropenem in children has been described. The most important covariates influencing the pharmacokinetics were weight and CLcr.
Reference: PAGE 3 () Abstr 852 [www.page-meeting.org/?abstract=852]
Poster: poster