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The pharmacokinetics of meropenem in surgical patients with moderate or severe infections
A M Lovering1, C J Vickery, D S Watkin
1Department of Medical Microbiology, Southmead Health Services NHS Trust, Westbury-on-Trym, Bristol, UK.
Abstract:
The pharmacokinetics of meropenem were studied in a group of 11 surgical patients (four male, seven female; mean age 63 years; mean weight 72 kg) all of whom had moderate or severe infection and who received a mean dose of 14.5 mg/kg +/- 2.7 meropenem 8-hourly iv for a minimum of 4 days. Venous blood samples were collected at timed intervals after the first dose on day 1 and the second dose on the fourth or fifth day of therapy. Serum meropenem concentrations were assayed by HPLC and fitted to a two compartment pharmacokinetic model. The mean pharmacokinetic parameters (+/- standard deviation) on day 1 were T1/2 84.6 +/- 24.1 min, Vdss 0.22 +/- 0.06 L/kg, AUC 6028 +/- 1983.2 mg.min/L, Cltot 188 +/- 67 mL/min and MRT 89.1 +/- 67.8 min. On the fourth or fifth days of therapy the values were T1/2 79.9 +/- 18.2 min, Vdss 0.17 +/- 0.8 L/kg, AUC 6000.7 +/- 2417 mg.min/L, Cltot 190 +/- 60 mL/min and MRT 67.8 +/- 30.4 min. Although the T1/2, Vdss and MRT decreased from day 1 to day 4 or 5 these changes were not statistically significant (Student's t-test, P > 0.05). Total clearance of meropenem was linearly related to creatinine clearance or patient age on the first day of therapy. Although the T1/2 and MRT were longer and the Cltot lower than those reported for young healthy volunteers, they were similar to those found in elderly volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
This study examined meropenem pharmacokinetics in surgical patients, finding no significant changes from day 1 to day 5. Meropenem clearance correlated with creatinine clearance and age, similar to elderly volunteers.
Area of Science:
- Pharmacokinetics
- Infectious Diseases
- Clinical Pharmacology
Background:
- Meropenem is a broad-spectrum carbapenem antibiotic used for severe infections.
- Understanding meropenem pharmacokinetics in surgical patients is crucial for optimizing dosing and treatment outcomes.
Purpose of the Study:
- To investigate the pharmacokinetic profile of meropenem in surgical patients with moderate to severe infections.
- To assess changes in meropenem pharmacokinetics over a 4-5 day treatment course.
- To explore relationships between meropenem clearance and patient factors like age and renal function.
Main Methods:
- 11 surgical patients received meropenem (14.5 mg/kg 8-hourly IV) for at least 4 days.
- Serum meropenem concentrations were measured via HPLC after the first and fourth/fifth day doses.
- Data were analyzed using a two-compartment pharmacokinetic model.
Main Results:
- Pharmacokinetic parameters (T1/2, Vdss, AUC, Cltot, MRT) were determined on day 1 and day 4/5.
- No statistically significant changes in T1/2, Vdss, or MRT were observed between day 1 and day 4/5 (P > 0.05).
- Total meropenem clearance showed a linear relationship with creatinine clearance and patient age on day 1.
Conclusions:
- Meropenem pharmacokinetics in surgical patients with moderate to severe infections remain relatively stable over a 4-5 day treatment period.
- Observed pharmacokinetic parameters were comparable to those in elderly volunteers, suggesting age and renal function influence meropenem disposition.
- These findings support the established dosing regimen for meropenem in this patient population.