Pivmecillinam

Pivmecillinam

Systematic (IUPAC) name
2,2-dimethylpropanoyloxymethyl (2S,5R,6R)-6-[(azepan-1-ylmethylene)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
Clinical data
AHFS/Drugs.com	Micromedex Detailed Consumer Information
Pregnancy cat.	B(US) Appears safe in pregnancy[1]
Legal status	℞ Prescription only
Routes	Oral
Pharmacokinetic data
Bioavailability	Low
Protein binding	5 to 10% (as mecillinam)
Metabolism	Pivmecillinam is hydrolyzed to mecillinam
Half-life	1 to 3 hours
Excretion	Renal and biliary, mostly as mecillinam
Identifiers
CAS number	32886-97-8 Y
ATC code	J01CA08
PubChem	CID 36272
ChemSpider	33356 N
UNII	1WAM1OQ30B Y
KEGG	D02889 Y
Chemical data
Formula	C21H33N3O5S
Mol. mass	439.569 g/mol
SMILES	eMolecules & PubChem
N(what is this?)  (verify)

Pivmecillinam (INN) or amdinocillin pivoxil (USAN, trade names Selexid, Penomax and Coactabs) is an orally-active prodrug of mecillinam, an extended-spectrum penicillin antibiotic. Pivmecillinam is the pivaloyloxymethyl ester of mecillinam. Neither drug is available in the United States.^[2]

Pivmecillinam is only considered to be active against Gram-negative bacteria, and is used primarily in the treatment of lower urinary tract infections. In the Nordic countries, pivmecillinam has been widely used in that indication since the 1970s. It has been proposed as the first-line drug of choice for empirical treatment of acute cystitis.^[1][3] It has also been used to treat paratyphoid fever.^[4]

Activity

See also: Mecillinam

Adverse effects

See also: Beta-lactam antibiotic: Adverse effects

The adverse effect profile of pivmecillinam is similar to that of other penicillins. The most common side effects of mecillinam use are rash and gastrointestinal upset, including nausea and vomiting.^[1][5]

Prodrugs that release pivalic acid when broken down by the body — such as pivmecillinam, pivampicillin and cefditoren pivoxil — have long been known to deplete levels of carnitine.^[6][7] This is not due to the drug itself, but to pivalate, which is mostly removed from the body by forming a conjugate with carnitine. Although short-term use of these drugs can cause a marked decrease in blood levels of carnitine,^[8] it is unlikely to be of clinical significance;^[7] long-term use, however, appears problematic and is not recommended.^[7][9][10]

References

1. ^ ^{a b c} Nicolle LE (August 2000). "Pivmecillinam in the treatment of urinary tract infections". J Antimicrob Chemother. 46 Suppl A (90001): 35–39. doi:10.1093/jac/46.suppl_1.35. PMID 10969050. http://jac.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=10969050. 
2. ^ Pham P, Bartlett JG (August 28, 2008). "Amdinocillin (Mecillinam)". Point-of-Care Information Technology ABX Guide. Johns Hopkins University. http://prod.hopkins-abxguide.org/antibiotics/antibacterial/pcn_others/amdinocillin__mecillinam_.html.  Retrieved on August 31, 2008. Freely available with registration.
3. ^ Graninger W (October 2003). "Pivmecillinam—therapy of choice for urinary tract infection". Int J Antimicrob Agents. 22 Suppl 2: 73–8. doi:10.1016/S0924-8579(03)00235-8. PMID 14527775. http://linkinghub.elsevier.com/retrieve/pii/S0924857903002358. 
4. ^ Tanphaichitra D, Srimuang S, Chiaprasittigul P, Menday P, Christensen OE (1984). "The combination of pivmecillinam and pivampicillin in the treatment of enteric fever". Infection 12 (6): 381–3. doi:10.1007/BF01645219. PMID 6569851. 
5. ^ "Selexid Tablets". electronic Medicines Compendium. June 5, 2008. http://emc.medicines.org.uk/emc/assets/c/html/DisplayDoc.asp?DocumentID=2566.  Retrieved on August 31, 2008.
6. ^ Holme E, Greter J, Jacobson CE, et al. (August 1989). "Carnitine deficiency induced by pivampicillin and pivmecillinam therapy". Lancet 2 (8661): 469–73. doi:10.1016/S0140-6736(89)92086-2. PMID 2570185. http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(89)92086-2. 
7. ^ ^{a b c} Brass EP (December 2002). "Pivalate-generating prodrugs and carnitine homeostasis in man". Pharmacol Rev 54 (4): 589–98. doi:10.1124/pr.54.4.589. PMID 12429869. http://pharmrev.aspetjournals.org/cgi/pmidlookup?view=long&pmid=12429869. 
8. ^ Abrahamsson K, Holme E, Jodal U, Lindstedt S, Nordin I (June 1995). "Effect of short-term treatment with pivalic acid containing antibiotics on serum carnitine concentration—a risk irrespective of age". Biochem. Mol. Med. 55 (1): 77–9. doi:10.1006/bmme.1995.1036. PMID 7551831. http://linkinghub.elsevier.com/retrieve/pii/S1077315085710368. 
9. ^ Holme E, Jodal U, Linstedt S, Nordin I (September 1992). "Effects of pivalic acid-containing prodrugs on carnitine homeostasis and on response to fasting in children". Scand J Clin Lab Invest 52 (5): 361–72. doi:10.3109/00365519209088371. PMID 1514015. 
10. ^ Makino Y, Sugiura T, Ito T, Sugiyama N, Koyama N (September 2007). "Carnitine-associated encephalopathy caused by long-term treatment with an antibiotic containing pivalic acid". Pediatrics 120 (3): e739–41. doi:10.1542/peds.2007-0339. PMID 17724113. 

Skeletal formula of mecillinam, the active moiety of pivmecillinam