Meropenem: pharmacologic advantages of clinical interest
Domínguez-Gil Hurlé, A.
Enfermedades Infecciosas y Microbiologia Clinica 15(Suppl 1): 32-37
1997
ISSN/ISBN: 0213-005X PMID: 9410067 Document Number: 475041
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.