Chemical formula: C₂₁H₃₃N₃O₅S Molecular mass: 439.569 g/mol PubChem compound: 115163
Pivmecillinam hydrochloride is an orally active antibiotic, containing the pro-drug pivmecillinam. This is the pivaloyloxymethylester of the amidinopenicillanic acid, mecillinam. On oral administration it is well absorbed and subsequently hydrolysed in the body to mecillinam, the active antibacterial agent, by non-specific esterases present in blood, gastro-intestinal mucosa and other tissues. Mecillinam is a betalactam with a narrow-spectrum of activity. It is mainly active against Gram-negative bacteria and works by interfering with the biosynthesis of the bacterial cell wall.
Mecillinam exerts high specificity against penicillin-binding protein 2 (PBP-2) in the Gram-negative cell wall, unlike the majority of other beta-lactam agents, which preferentially bind Gram-negative PBP-1A, -1B or -3. Synergy has been observed when mecillinam is combined with other beta-lactam antibiotics, including ampicillin, amoxicillin, cefoxitin, cefalotin, cefazolin, cefradine, cefamandole, ceftazidime and ceftriaxone, against selected isolates of most Enterobacteriaceae.
Pivmecillinam has low impact on the normal skin, oral, intestinal and vaginal microflora.
As a narrow-spectrum antibiotic active against Gram-negative bacilli, pivmecillinam is unlikely to contribute to the widespread of resistant bacterial strains. The exclusive action of pivmecillinam on PBP-2 results in the low cross-resistance with other beta-lactams (penicillins and cephalosporins). Mecillinam has limited susceptibility to most of the beta-lactamases (including ESBL) produced by Enterobacteriaceae. In Enterobacteriaceae, resistance to mecillinam may be due to marked production of some beta-lactamases and modification of penicillin binding proteins.
EUCAST: S≤8 mg/L / R>8 mg/L (for E. coli, Klebsiella spp. and P. mirabilis)
Gram negative microorganisms:
Enterobacter spp.
Escherichia coli
Klebsiella spp.
Proteus mirabilis
Gram positive microorganisms:
Enterococcus faecalis
Enterococcus faecium
Staphylococcus saprophyticus*
Gram negative microorganisms:
Pseudomonas spp.
* Due to the high concentrations of mecillinam in urine, clinical effect is normally obtained in acute uncomplicated cystitis caused by S. saprophyticus.
As a beta-lactam antibiotic, the bacteriological effect of Pivmecillinam hydrochloride in the treatment of acute uncomplicated cystitis is expected to depend on time above MIC.
Pivmecillinam hydrochloride is the pro-drug of mecillinam that is hydrolysed in the body to mecillinam, the active antibacterial agent.
Following oral administration of 400 mg pivmecillinam peak concentrations of approximately 3 μg/mL is attained within 1-1½ hours after dosing. The bioavailability of orally administered pivmecillinam is approximately 60-70%. Bioavailability of Pivmecillinam hydrochloride tablets is not affected by taking the tablets with food.
The elimination half-life of mecillinam is about 1 hour. It is excreted primarily in the urine with some biliary excretion. Mecillinam is to a large extent excreted by the kidneys by filtration and active tubular secretion. Probenecid, which inhibits tubular secretion, also inhibits the elimination of mecillinam. Approximately 60-70% of the mecillinam reaching the systemic circulation is excreted unchanged in urine; almost all within the first 6 hours after dosing resulting in urine concentrations >200 mg/L after oral administration of one 400 mg tablet.
The elimination of mecillinam is reduced by approximately 75% in patients with severe renal impairment.
Low concentrations of mecillinam are observed in foetuses, breast milk, and amniotic fluid. The protein binding of mecillinam in human serum is 5-10%.
Mecillinam displays linear pharmacokinetics in the clinically relevant range.
Gender differences in the pharmacokinetics of mecillinam have not been reported.
Clinically relevant accumulation of mecillinam does not take place at dosing up to four times daily and there are no indications that the pharmacokinetics change over time during repeated dosing.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, toxicity to reproduction and development. No genotoxicity or carcinogenicity studies have been performed with pivmecillinam or the active drug mecillinam.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
