Tebipenem

Chemical compound

J01DH06 (WHO)

Legal statusLegal status

Prescription-only in Japan; investigational elsewhere

Identifiers

IUPAC name

(4R,5S,6S)-(Pivaloyloxy)methyl 3-((1-(4,5-dihydrothiazol-2-yl)azetidin-3-yl)thio)-6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate

CAS Number

161715-24-8^N

UNII

95AK1A52I8

KEGG

D09598

PDB ligand

1TE (PDBe, RCSB PDB)

CompTox Dashboard (EPA)

DTXSID00167228

Chemical and physical dataFormulaC₂₂H₃₁N₃O₆S₂Molar mass497.63 g·mol⁻¹3D model (JSmol)

Interactive image

SMILES

[H][C@]12N(C(C(OCOC(C(C)(C)C)=O)=O)=C(SC3CN(C4=NCCS4)C3)[C@@H]2C)C([C@@]1([C@H](O)C)[H])=O

Tebipenem (brand name Orapenem) is a broad-spectrum orally-administered antibiotic, from the carbapenem subgroup of β-lactam antibiotics. It was developed as a replacement drug to combat bacteria that had acquired antibiotic resistance to commonly used antibiotics.^[1]^[2] Tebipenem is formulated as the ester tebipenem pivoxil due to the better absorption and improved bioavailability of this form.^[3] It has performed well in clinical trials for ear infection and looks likely to be further developed in future.^[4] It is only marketed in Japan.^[5] Tebipenem is the first carbapenem whose prodrug form, the pivalyl ester, is orally available.^[6]

References

^ El-Gamal MI, Oh CH (2010). "Current status of carbapenem antibiotics". Current Topics in Medicinal Chemistry. 10 (18): 1882–97. doi:10.2174/156802610793176639. PMID 20615191.
^ Fujimoto K, Takemoto K, Hatano K, Nakai T, Terashita S, Matsumoto M, et al. (February 2013). "Novel carbapenem antibiotics for parenteral and oral applications: in vitro and in vivo activities of 2-aryl carbapenems and their pharmacokinetics in laboratory animals". Antimicrobial Agents and Chemotherapy. 57 (2): 697–707. doi:10.1128/AAC.01051-12. PMC 3553697. PMID 23147735.
^ Kato K, Shirasaka Y, Kuraoka E, Kikuchi A, Iguchi M, Suzuki H, et al. (October 2010). "Intestinal absorption mechanism of tebipenem pivoxil, a novel oral carbapenem: involvement of human OATP family in apical membrane transport". Molecular Pharmaceutics. 7 (5): 1747–56. doi:10.1021/mp100130b. PMID 20735088.
^ Sugita R (June 2013). "Good transfer of tebipenem into middle ear effusion conduces to the favorable clinical outcomes of tebipenem pivoxil in pediatric patients with acute otitis media". Journal of Infection and Chemotherapy. 19 (3): 465–71. doi:10.1007/s10156-012-0513-5. PMID 23393013. S2CID 1228827.
^ Rossi S, ed. (7 August 2014). "Tebipenem Pivoxil". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. Retrieved 6 April 2015.
^ Hazra S, Xu H, Blanchard JS (June 2014). "Tebipenem, a new carbapenem antibiotic, is a slow substrate that inhibits the β-lactamase from Mycobacterium tuberculosis". Biochemistry. 53 (22): 3671–8. doi:10.1021/bi500339j. PMC 4053071. PMID 24846409.

Antibacterials active on the cell wall and envelope (J01C-J01D)

Beta-lactams
(inhibit synthesis
of peptidoglycan
layer of bacterial
cell wall by binding
to and inhibiting
PBPs, a group of
D-alanyl-D-alanine
transpeptidases)

Penicillins (Penams)

Narrow
spectrum

β-lactamase sensitive (1st generation)	Benzylpenicillin (G)^# Benzathine benzylpenicillin^# Procaine benzylpenicillin^# Phenoxymethylpenicillin (V)^# Propicillin^‡ Pheneticillin^‡ Azidocillin^‡ Clometocillin^‡ Penamecillin^‡
β-lactamase resistant (2nd generation)	Cloxacillin^# (Dicloxacillin Flucloxacillin) Oxacillin Nafcillin Methicillin^‡

Extended
spectrum

Aminopenicillins (3rd generation)	Amoxicillin^# Ampicillin^# (Pivampicillin Hetacillin^‡ Bacampicillin^‡ Lenampicillin Metampicillin^‡ Talampicillin^‡) Epicillin^‡
Carboxypenicillins (4th generation)	Ticarcillin Carbenicillin^‡ / Carindacillin^‡ Temocillin^‡
Ureidopenicillins (4th generation)	Piperacillin Azlocillin^‡ Mezlocillin^‡
Other	Mecillinam (Pivmecillinam) Sulbenicillin^‡

Carbapenems / Penems

Cephems
Cephalosporins
Cephamycins
Carbacephems

1st generation	Cefazolin^# Cefalexin ^# Cefadroxil Cefapirin Cefazedone^‡ Cefazaflur^‡ Cefradine^‡ Cefroxadine^‡ Ceftezole^‡ Cefaloglycin^‡ Cefacetrile^‡ Cefalonium^‡ Cefaloridine^‡ Cefalotin Cefatrizine^‡
2nd generation	Cefaclor Cefprozil Cefuroxime Cefuroxime axetil Cefamandole^‡ Cefonicid^‡ Ceforanide^‡ Cefuzonam^‡ Cephamycin (Cefoxitin Cefotetan Cefminox^‡ Cefbuperazone^‡ Cefmetazole^‡) Carbacephem (Loracarbef^‡)
3rd generation	Cefixime^# Ceftriaxone^# Cefotaxime^# Antipseudomonal (Ceftazidime^# Cefoperazone) Cefdinir Cefcapene Cefdaloxime Ceftizoxime Cefmenoxime Cefpiramide Cefpodoxime Ceftibuten Cefditoren Cefotiam^‡ Cefetamet^‡ Cefodizime^‡ Cefpimizole^‡ Cefsulodin^‡ Cefteram^‡ Ceftiolene^‡ Oxacephem (Flomoxef Latamoxef^‡)
4th generation	Cefepime Cefozopran^‡ Cefpirome Cefquinome^‡
5th generation	Ceftaroline fosamil Ceftolozane Ceftobiprole
Siderophore	Cefiderocol^#
Veterinary	Ceftiofur Cefquinome Cefovecin

Monobactams

β-lactamase inhibitors

Combinations

Polypeptides

Glycopeptides Lipoglycopeptides	Inhibit PG chain elongation: Vancomycin^# (Oritavancin Telavancin) Teicoplanin (Dalbavancin) Ristocetin^‡ Avoparcin Inhibit autolysin: Corbomycin (not approved)
Lipopeptides	Insert into bacterial cell wall causing perforation and depolarization: Daptomycin Surfactin
Polymyxins	Bind to LPS in the outer bacterial membrane, acting in detergent-like fashion: Colistin Polymyxin B
Other	Inhibits PG elongation and crosslinking: Ramoplanin^§