Pivampicillin

Last updated
Pivampicillin
Pivampicillin.svg
Clinical data
AHFS/Drugs.com Micromedex Detailed Consumer Information
Routes of
administration
Oral
ATC code
Pharmacokinetic data
Excretion Renal (76%)
Identifiers
  • 2,2-Dimethylpropanoyloxymethyl (2S,5R,6R)-6-{[(2R)-2-amino-2-phenyl-acetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.046.975 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C22H29N3O6S
Molar mass 463.55 g·mol−1
3D model (JSmol)
  • O=C(OCOC(=O)C(C)(C)C)[C@@H]2N3C(=O)[C@@H](NC(=O)[C@@H](c1ccccc1)N)[C@H]3SC2(C)C
  • InChI=1S/C22H29N3O6S/c1-21(2,3)20(29)31-11-30-19(28)15-22(4,5)32-18-14(17(27)25(15)18)24-16(26)13(23)12-9-7-6-8-10-12/h6-10,13-15,18H,11,23H2,1-5H3,(H,24,26)/t13-,14-,15+,18-/m1/s1 Yes check.svgY
  • Key:ZEMIJUDPLILVNQ-ZXFNITATSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Pivampicillin is a pivaloyloxymethyl ester of ampicillin. It is a prodrug, which is thought to enhance the oral bioavailability of ampicillin because of its greater lipophilicity compared to that of ampicillin.

Contents

Adverse effects

Prodrugs that release pivalic acid when broken down by the body—such as pivampicillin, pivmecillinam, and cefditoren pivoxil—have long been known to deplete levels of carnitine. [1] [2] This effect 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, [3] it is unlikely to be of clinical significance; [2] long-term use, however, is not recommended. [2] [4] [5]

Availability

Worldwide, pivampicillin is only available in Denmark, where it is sold as Pondocillin® by PharmaCoDane, or Miraxid® by LEO Pharma. [6]

Related Research Articles

<span class="mw-page-title-main">Ampicillin</span> Antibiotic

Ampicillin is an antibiotic belonging to the aminopenicillin class of the penicillin family. The drug is used to prevent and treat a number of bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, salmonellosis, and endocarditis. It may also be used to prevent group B streptococcal infection in newborns. It is used by mouth, by injection into a muscle, or intravenously.

<span class="mw-page-title-main">Amoxicillin</span> Beta-lactam antibiotic

Amoxicillin is an antibiotic medication belonging to the aminopenicillin class of the penicillin family. The drug is used to treat bacterial infections such as middle ear infection, strep throat, pneumonia, skin infections, odontogenic infections, and urinary tract infections. It is taken by mouth, or less commonly by injection.

<span class="mw-page-title-main">Chloramphenicol</span> Antibiotic

Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections. This includes use as an eye ointment to treat conjunctivitis. By mouth or by injection into a vein, it is used to treat meningitis, plague, cholera, and typhoid fever. Its use by mouth or by injection is only recommended when safer antibiotics cannot be used. Monitoring both blood levels of the medication and blood cell levels every two days is recommended during treatment.

<span class="mw-page-title-main">Valproate</span> Medication used for epilepsy, bipolar disorder and migraine

Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those with absence seizures, partial seizures, and generalized seizures. They can be given intravenously or by mouth, and the tablet forms exist in both long- and short-acting formulations.

<span class="mw-page-title-main">Carnitine</span> Amino acid active in mitochondria

Carnitine is a quaternary ammonium compound involved in metabolism in most mammals, plants, and some bacteria. In support of energy metabolism, carnitine transports long-chain fatty acids from the cytosol into mitochondria to be oxidized for free energy production, and also participates in removing products of metabolism from cells. Given its key metabolic roles, carnitine is concentrated in tissues like skeletal and cardiac muscle that metabolize fatty acids as an energy source. Generally individuals, including strict vegetarians, synthesize enough L-carnitine in vivo.

<i>Enterococcus faecalis</i> Species of bacterium

Enterococcus faecalis – formerly classified as part of the group D Streptococcus system – is a Gram-positive, commensal bacterium inhabiting the gastrointestinal tracts of humans. Like other species in the genus Enterococcus, E. faecalis is found in healthy humans and can be used as a probiotic. The probiotic strains such as Symbioflor1 and EF-2001 are characterized by the lack of specific genes related to drug resistance and pathogenesis. As an opportunistic pathogen, E. faecalis can cause life-threatening infections, especially in the nosocomial (hospital) environment, where the naturally high levels of antibiotic resistance found in E. faecalis contribute to its pathogenicity. E. faecalis has been frequently found in reinfected, root canal-treated teeth in prevalence values ranging from 30% to 90% of the cases. Re-infected root canal-treated teeth are about nine times more likely to harbor E. faecalis than cases of primary infections.

Ampicillin/sulbactam is a fixed-dose combination medication of the common penicillin-derived antibiotic ampicillin and sulbactam, an inhibitor of bacterial beta-lactamase. Two different forms of the drug exist. The first, developed in 1987 and marketed in the United States under the brand name Unasyn, generic only outside the United States, is an intravenous antibiotic. The second, an oral form called sultamicillin, is marketed under the brand name Ampictam outside the United States, and generic only in the United States. Ampicillin/sulbactam is used to treat infections caused by bacteria resistant to beta-lactam antibiotics. Sulbactam blocks the enzyme which breaks down ampicillin and thereby allows ampicillin to attack and kill the bacteria.

<span class="mw-page-title-main">Sultamicillin</span> Chemical compound

Sultamicillin, sold under the brand name Unasyn among others, is an oral form of the penicillin antibiotic combination ampicillin/sulbactam. It is used for the treatment of bacterial infections of the upper and lower respiratory tract, the kidneys and urinary tract, skin and soft tissues, among other organs. It contains esterified ampicillin and sulbactam.

Pivalic acid is a carboxylic acid with a molecular formula of (CH3)3CCO2H. This colourless, odiferous organic compound is solid at room temperature. Two abbreviation for pivalic acid are t-BuC(O)OH and PivOH. The pivalyl or pivaloyl group is abbreviated t-BuC(O).

<span class="mw-page-title-main">Cefditoren</span> Chemical to treat skin infections

Cefditoren, also known as cefditoren pivoxil is an antibiotic used to treat infections caused by Gram-positive and Gram-negative bacteria that are resistant to other antibiotics. It is mainly used for treatment of community acquired pneumonia. It is taken by mouth and is in the cephalosporin family of antibiotics, which is part of the broader beta-lactam group of antibiotics.

<span class="mw-page-title-main">Gamma-butyrobetaine dioxygenase</span> Protein-coding gene in the species Homo sapiens

Gamma-butyrobetaine dioxygenase is an enzyme that in humans is encoded by the BBOX1 gene. Gamma-butyrobetaine dioxygenase catalyses the formation of L-carnitine from gamma-butyrobetaine, the last step in the L-carnitine biosynthesis pathway. Carnitine is essential for the transport of activated fatty acids across the mitochondrial membrane during mitochondrial beta oxidation. In humans, gamma-butyrobetaine dioxygenase can be found in the kidney (high), liver (moderate), and brain. BBOX1 has recently been identified as a potential cancer gene based on a large-scale microarray data analysis.

<span class="mw-page-title-main">Pivaloyloxymethyl</span>

Pivaloyloxymethyl (POM, pivoxil, pivoxyl) is a protecting group used in organic synthesis. The POM radical has the formula (CH3)3C-CO-O-CH2.

<span class="mw-page-title-main">Droxidopa</span> Synthetic amino acid/norepinephrine prodrug

Droxidopa is a synthetic amino acid precursor which acts as a prodrug to the neurotransmitter norepinephrine (noradrenaline). Unlike norepinephrine, droxidopa is capable of crossing the protective blood–brain barrier (BBB).

<span class="mw-page-title-main">Mecillinam</span> Pharmaceutical drug

Mecillinam (INN) or amdinocillin (USAN) is an extended-spectrum penicillin antibiotic of the amidinopenicillin class that binds specifically to penicillin binding protein 2 (PBP2), and is only considered to be active against Gram-negative bacteria. It is used primarily in the treatment of urinary tract infections, and has also been used to treat typhoid and paratyphoid fever. Because mecillinam has very low oral bioavailability, an orally active prodrug was developed: pivmecillinam.

<span class="mw-page-title-main">Pivmecillinam</span> Chemical compound

Pivmecillinam (INN) or amdinocillin pivoxil is an orally active prodrug of mecillinam, an extended-spectrum penicillin antibiotic. Pivmecillinam is the pivaloyloxymethyl ester of mecillinam.

<span class="mw-page-title-main">Ciclacillin</span> Chemical compound

Ciclacillin (INN) or cyclacillin (USAN), trade names Cyclapen, Cyclapen-W, Vastcillin, and others, is an aminopenicillin antibiotic. Its spectrum of activity is similar to that of ampicillin, although it is less susceptible to beta-lactamases than ampicillin and has much higher bioavailability. A large randomized, double-blind clinical trial published in 1978 also showed that ciclacillin is associated with significantly fewer and milder adverse effects than ampicillin; later studies seemed to confirm this improved tolerability, at least in children.

<span class="mw-page-title-main">Gabapentin enacarbil</span> Gabapentin prodrug used to treat restless legs syndrome and shingles complications

Gabapentin enacarbil is an anticonvulsant and analgesic drug of the gabapentinoid class, and a prodrug to gabapentin. It was designed for increased oral bioavailability over gabapentin, and human trials showed it to produce extended release of gabapentin with almost twice the overall bioavailability, especially when taken with a fatty meal. Gabapentin enacarbil has passed human clinical trials for the treatment of restless legs syndrome, and initial results have shown it to be well tolerated and reasonably effective.

Etomoxir, or 2[6(4-chlorophenoxy)hexyl]oxirane-2-carboxylate, is an irreversible inhibitor of carnitine palmitoyltransferase-1 (CPT-1) on the inner face of the outer mitochondrial membrane. This prevents the formation of acyl carnitines, a step that is necessary for the transport of fatty acyl chains from the cytosol into the intermembrane space of the mitochondria. This step is essential to the production of ATP from fatty acid oxidation. Etomoxir has also been identified as a direct agonist of PPARα. An off-target effect has been demonstrated at high concentrations of etomoxir on Coenzyme-A (CoA) metabolism.

<span class="mw-page-title-main">Estradiol pivalate</span> Chemical compound

Estradiol pivalate, also known as estradiol trimethyl acetate (E2-TMA) and sold under the brand name Estrotate, is an estrogen medication and an estrogen ester; specifically, a pivalic acid ester of estradiol. Literature sources are conflicting as to whether the ester is located at the C3 position or at the C17β position. It was marketed as an oil solution for intramuscular injection in the 1940s and 1950s. A combination of estradiol pivalate (1 mg/mL) and progesterone (10 mg/mL) in oil solution for intramuscular injection was available in 1949. An aqueous suspension of estradiol pivalate was also developed by 1950 although whether it was ever marketed is unclear.

References

  1. Holme E, Greter J, Jacobson CE, Lindstedt S, Nordin I, Kristiansson B, Jodal U (August 1989). "Carnitine deficiency induced by pivampicillin and pivmecillinam therapy". Lancet. 2 (8661): 469–473. doi:10.1016/S0140-6736(89)92086-2. PMID   2570185. S2CID   31555161.
  2. 1 2 3 Brass EP (December 2002). "Pivalate-generating prodrugs and carnitine homeostasis in man". Pharmacological Reviews. 54 (4): 589–598. doi:10.1124/pr.54.4.589. PMID   12429869. S2CID   14507215.
  3. 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". Biochemical and Molecular Medicine. 55 (1): 77–79. doi:10.1006/bmme.1995.1036. PMID   7551831.
  4. 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". Scandinavian Journal of Clinical and Laboratory Investigation. 52 (5): 361–372. doi:10.3109/00365519209088371. PMID   1514015.
  5. 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–e741. doi:10.1542/peds.2007-0339. PMID   17724113. S2CID   40136171.
  6. "Pondocillin®" . Retrieved 2016-09-18.