Pharmacokinetics of meropenem compared to imipenem-cilastatin in young, healthy males

Abstract

Imipenem combined with cilastatin and meropenem was given as intravenous infusions of 1 g to eight young, healthy males on two separate occasions. Blood and urine samples were collected for up to 12 h. The terminal half-lives in plasma were 0.98 h and 1.11 h for meropenem and imipenem, respectively. The volume of distribution was smaller for meropenem than for imipenem (12.5 l and 14.4 l, respectively). The plasma clearance for meropenem was 188 (SD 31) ml/min and for imipenem 183 (SD 25) ml/min. Renal clearance was on average 139 (SD 24) ml/min and 135 (SD 11) ml/min, respectively. About 75% of the administered dose of both compounds was eliminated unchanged in urine. Non-renal clearance accounted for approximately 25% of the total clearance for both drugs. The kinetics of meropenem are very similar to those of imipenem given with cilastatin, and meropenem is as stable against renal metabolic degradation as imipenem combined with cilastatin.

Meropenem versus imipenem/cilastatin in intra-abdominal infections requiring surgery

“…The pharmacokinetic properties of meropenem and imipenem administered as imipenem/cilastatin are comparable, following single and multiple dose administration (Nilsson-Ehle et al, 1991;Drusano, Yuen & Standiford, 1992) and, therefore, the same dosing regimen (1 g every 8 h) was employed for both antibiotics.…”

Randomized comparison of meropenem with cefotaxime for treatment of bacterial meningitis. Meropenem Meningitis Study Group

“…Meropenem, a carbapenem structurally related to imipenem, is stable to the majority of ␤-lactamases (23) and is active in vitro against a broad range of gram-negative and gram-positive aerobic and anaerobic bacteria, with several-fold-greater activity than that of imipenem against H. influenzae and N. meningitidis (4). Meropenem is also stable to human renal dehydropeptidase-I and, unlike imipenem, does not need to be combined with a dehydropeptidase inhibitor such as cilastatin (22).…”

Postantibiotic Leukocyte Enhancement of Meropenem against Gram-Positive and Gram-Negative Strains

“…Usually, these antibiotics produce a PAE only against gram-positive strains and have a short or no PAE on gram-negative rods (22). On the contrary, different authors have demonstrated that carbapenems induce a consistent PAE both in vitro and in vivo against both grampositive and gram-negative strains, including Pseudomonas aeruginosa (1,3,6,7,15,18).…”

“…Usually, these antibiotics produce a PAE only against gram-positive strains and have a short or no PAE on gram-negative rods (22). On the contrary, different authors have demonstrated that carbapenems induce a consistent PAE both in vitro and in vivo against both grampositive and gram-negative strains, including Pseudomonas aeruginosa (1,3,6,7,15,18).Meropenem is a new carbapenem which differs from imipenem in having a dimethylcarbamoylpyrrolidinethio side chain at C-2 which assures it a broad spectrum of activity against aerobes and anaerobes (9, 17). This carbapenem derivative has a pharmacokinetic profile very similar to that of imipenem and a consistent PAE even greater than that of imipenem (3,7,15,18).…”

“…This carbapenem derivative has a pharmacokinetic profile very similar to that of imipenem and a consistent PAE even greater than that of imipenem (3,7,15,18). Therefore, the aim of this study was to investigate the occurrence of a PALE of meropenem against gram-positive and gram-negative pathogens in comparison to imipenem, which may be considered the reference drug among carbapenems.…”