| Abstrakt: |
Amoxicillin plasma concentrations, pharmacokinetic parameters, and the influence of demographic, anthropometric, and clinical covariates were investigated in 150 neonates. Gestational age (GA) ranged from 25 to 42 weeks and mean postnatal age (PNA) was 0.8 days. Amoxicillin concentrations were measured with reversed-phase HPLC in surplus plasma from routine assays of coadministered gentamicin. Mean total body clearance corrected for body weight (CLW) was 0.096±0.036 Lkg−1h−1, mean elimination half-life (t12) was 5.2±1.9 hours, and mean volume of distribution corrected for body weight (VW) was 0.65±0.13 Lkg. Multiple regression equations were calculated for the prediction of CLW amoxicillin. CLW gentamicin, VW gentamicin, and GA were significant predictors of CLW amoxicillin. Amoxicillin peak and trough concentrations after the second dose and the time the concentration exceeds the minimum inhibitory concentration (T>MIC), reached with the current dosage regimen, were evaluated. Toxic plasma concentrations were reached in several patients. Therefore, the authors have proposed a lower dosage regimen, based on GA, population pharmacokinetic parameters, bacterial susceptibility (T>MIC), and possible toxicity 15 mgkg per 8 hours and 20 mgkg per 8 hours for neonates with GA 34 and GA>34 weeks, respectively. Simulation with this new dosage regimen indicated that satisfactory plasma concentrations were reached in all 150 neonates. Therefore, use of therapeutic drug monitoring and pharmacokinetic calculations for dosage adjustment is generally not necessary. |
