Abstract
Objectives: Since glomerular filtration rate (GFR) is responsible for the elimination of a large number of water-soluble drugs [1], the aim of this study was to develop a semi-physiological function for GFR maturation from neonates to adults.
Methods: In the pharmacokinetic analysis (NONMEM VI) based on data of gentamicin, tobramycin and vancomycin collected in 1760 patients (age 1 day-18 years, bodyweight 415g-85kg), a distinction was made between drug-specific and system-specific information. Since the maturational model for clearance is considered to contain system-specific information on the developmental changes in GFR [2], one GFR maturational function was derived for all three drugs.
Results: Simultaneous analysis of these three drugs showed that maturation of GFR mediated clearance from preterm neonates to adults was best described by a bodyweight-dependent exponent (BDE) function with an exponent varying from 1.4 in neonates to 1.0 in adults (Cl GFR = Cl drug *(BW/4kg) BDE with BDE=2.23*BW -0.065 ). Population clearance values (Cl drug ) for gentamicin, tobramycin and vancomycin were 0.21L/h, 0.28L/h and 0.39L/h for a full term neonate of 4kg, respectively.
Conclusions: Based on an integrated analysis of gentamicin, tobramycin and vancomycin, a semi-physiological function for GFR mediated clearance was derived that can potentially be used to establish evidence based dosing regimens of renally excreted drugs in children.
| Original language | American English |
|---|---|
| Journal | Abstracts of the Annual Meeting of the Population Approach Group in Europe |
| State | Published - Jun 2014 |
| Event | 2014 Meeting of the Population Approach Group in Europe - Cruise Terminal, Alicante, Spain Duration: Jun 10 2014 → Jun 13 2014 Conference number: 23 https://www.page-meeting.org/default.asp?id=38&keuze=meeting |
Keywords
- antibiotics
- developmental changes
- glomerular filtration
- pediatric age range
Disciplines
- Pediatrics