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[Meropenem: pharmacologic advantages of clinical interest]
1Servicio de Farmacia, Hospital Clínico, Salamanca.
Abstract:
The pharmacokinetic profile of meropenem is similar to that of imipenem/cilastatin. It differs in resistance to hydrolysis by the methaloenzyme, dehydropeptidase I, and therefore does not require the combination of cilastatin, being administered alone. Similar to other beta-lactamic drugs, it is mainly distributed in the extravascular space (apparent Vd, 21 I) with an half life of elimination of approximately one hour. A low proportion binds to plasma proteins (< 20%). The tissue concentrations are maintained for prolonged periods at values greater than the MIC of most pathogens. In LCR and aqueous humor it has limited penetration. Nonetheless, the levels achieved in patients with meningitis (40 mg/kg/8 h) range between 0.9 and 6.5 micrograms/ml, greater than the MIC of most pathogens associated with this disease. The renal clearance of meropenem surpasses that of creatinine, thereby indicating excretion by glomerular filtration and tubular secretion. The doses in patients with renal insufficiency should be reduced according to creatinine clearance. Modification of the dosage is not necessary in patients with hepatic failure. Administered at a doses of 1 g/8 hours meropenem presented a value of (AUICo infinity) 60-90 micrograms/h/ml. The (AUIC)24 = 125 ensures that the serum concentrations are maintained above 3 micrograms/ml during a period greater than 80% of the dosage interval.
Insights
Meropenem, a broad-spectrum antibiotic, offers a favorable pharmacokinetic profile. It is administered alone, unlike imipenem/cilastatin, and maintains effective therapeutic concentrations against most pathogens.
Area of Science:
- Pharmacology
- Infectious Diseases
- Antibiotic Therapy
Background:
- Meropenem shares pharmacokinetic similarities with imipenem/cilastatin but is resistant to dehydropeptidase I hydrolysis.
- This resistance allows meropenem to be administered alone, without the need for cilastatin.
Purpose of the Study:
- To elucidate the pharmacokinetic profile of meropenem.
- To compare its distribution, elimination, and penetration into specific body fluids.
- To determine appropriate dosing strategies based on renal and hepatic function.
Main Methods:
- Analysis of meropenem's distribution (apparent Vd) and elimination half-life.
- Assessment of plasma protein binding and tissue concentration.
- Evaluation of penetration into cerebrospinal fluid (CSF) and aqueous humor.
- Determination of renal and hepatic clearance.
- Calculation of pharmacokinetic parameters like Area Under the Curve (AUC) and time above Minimum Inhibitory Concentration (MIC).
Main Results:
- Meropenem distributes primarily to the extravascular space with an elimination half-life of approximately one hour.
- Low plasma protein binding (<20%) and sustained tissue concentrations exceeding MIC for most pathogens.
- Limited penetration into CSF and aqueous humor, but therapeutic levels achieved in meningitis patients.
- Renal clearance exceeds creatinine clearance, indicating glomerular filtration and tubular secretion.
- Dosing adjustments are necessary for renal insufficiency but not for hepatic failure.
Conclusions:
- Meropenem exhibits favorable pharmacokinetics, allowing for monotherapy.
- Achieves therapeutic concentrations in tissues and relevant body fluids, including CSF in meningitis.
- Dosing requires consideration of renal function, highlighting its importance in meropenem therapy.