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Pharmacokinetics of meropenem in febrile neutropenic patients. Swedish study group
A Nyhlén1, B Ljungberg, I Nilsson-Ehle
1Department of Infectious Diseases, University Hospital of Lund, Sweden.
Abstract:
To determine the impact of neutropenia on the pharmacokinetics of meropenem, 14 patients with fever and neutropenia were given 1 g of meropenem i.v. every 8 h as an infusion over 30 min. The volume of distribution (16.2 l/1.73 m2) and the nonrenal clearance [75 ml/(min x 1.73 m2)] in this group were significantly increased compared to healthy subjects studied previously with identical techniques. The kinetic study was repeated when the patients had a normal temperature and a raised neutrophil count; most kinetic variables did not differ from the findings on the first day of treatment. The pharmacokinetic profile of meropenem in febrile neutropenic patients differs from earlier findings in healthy subjects. Considering these data and known minimum inhibitory concentration values for common pathogens, meropenem administered every 6 to 8 h seems an appropriate regimen in patients with febrile neutropenia. The shorter time interval may be used for treatment of Pseudomonas infection.
Insights
Neutropenia significantly alters meropenem pharmacokinetics, increasing its volume of distribution and nonrenal clearance in patients with fever and neutropenia. Dosing every 6-8 hours is recommended for effective treatment.
Area of Science:
- Pharmacology
- Infectious Diseases
- Clinical Pharmacy
Background:
- Neutropenia is a common side effect of chemotherapy and other conditions.
- Fever in neutropenic patients requires prompt and effective antibiotic treatment.
- Meropenem is a broad-spectrum carbapenem antibiotic used to treat serious bacterial infections.
Purpose of the Study:
- To investigate the pharmacokinetic profile of meropenem in patients with fever and neutropenia.
- To compare meropenem pharmacokinetics in neutropenic patients with those in healthy subjects.
- To determine an appropriate meropenem dosing regimen for febrile neutropenic patients.
Main Methods:
- A pharmacokinetic study was conducted in 14 patients with fever and neutropenia.
- Meropenem (1 g IV over 30 min every 8 h) was administered.
- Pharmacokinetic parameters were assessed during neutropenia and after recovery.
Main Results:
- The volume of distribution and nonrenal clearance of meropenem were significantly increased in febrile neutropenic patients compared to healthy subjects.
- Most pharmacokinetic variables remained consistent after neutrophil count recovery.
- The pharmacokinetic profile in neutropenic patients differed from that in healthy individuals.
Conclusions:
- Meropenem pharmacokinetics are altered in febrile neutropenic patients.
- An every 6- to 8-hour dosing interval for meropenem appears appropriate for this population.
- A shorter interval may be considered for Pseudomonas infections.