Identification

Name
Pivampicillin
Accession Number
DB01604
Type
Small Molecule
Groups
Approved
Description

Pivalate ester analog of ampicillin.

Structure
Thumb
Synonyms
  • Ampicillin pivaloyloxymethyl ester
  • Pivaloylampicillin
  • Pivaloyloxymethyl ampicillinate
  • Pivampicilina
  • Pivampicilline
  • Pivampicillinum
External IDs
MK-191
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Pondocillin Pws 175mg/5mlPowder, for solution175 mgOralLeo Pharma1989-12-312006-10-13Canada
Pondocillin Tab 500mgTablet500 mgOralLeo Pharma1984-12-312008-03-28Canada
International/Other Brands
Pondocillin
Categories
UNII
0HLM346LL7
CAS number
33817-20-8
Weight
Average: 463.547
Monoisotopic: 463.177706365
Chemical Formula
C22H29N3O6S
InChI Key
ZEMIJUDPLILVNQ-ZXFNITATSA-N
InChI
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
IUPAC Name
[(2S,5R,6R)-6-[(2R)-2-amino-2-phenylacetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carbonyloxy]methyl 2,2-dimethylpropanoate
SMILES
[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)[C@H](N)C1=CC=CC=C1)C(=O)OCOC(=O)C(C)(C)C

Pharmacology

Indication

or the treatment of respiratory tract infections (including acute bronchitis, acute exacerbations of chronic bronchitis and pneumonia); ear, nose and throat infections; gynecological infections; urinary tract infections (including acute uncomplicated gonococcal urethritis) when caused by non penicillinase-producing susceptible strains of the following organisms: gram-positive organisms, e.g., streptococci, pneumococci and staphylococci; gram-negative organisms, e.g., H. influenzae, N. gonorrhoeae, E. coli, P. mirabilis.

Pharmacodynamics

Pivampicillin is the pivaloyloxymethyl ester of (the semi-synthetic penicillin) ampicillin. It is an inactive pro-drug, which is converted during its absorption from the gastrointestinal tract to the microbiologically active ampicillin, together with formaldehyde and pivalic acid, by non-specific esterases present in most body tissues. Amounts in excess of 99% of the pivampicillin absorbed are converted to ampicillin within 15 minutes of absorption.

Mechanism of action

Ampicillin (the active metabolite of pivampicillin) has a bactericidal action resulting from inhibition of cell wall mucopeptide biosynthesis.

TargetActionsOrganism
APenicillin-binding protein 1A
inhibitor
Clostridium perfringens (strain 13 / Type A)
Absorption

Absorbed following oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

Approximately 1 hour.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcenocoumarolPivampicillin may increase the anticoagulant activities of Acenocoumarol.Approved, Investigational
AmikacinThe serum concentration of Amikacin can be decreased when it is combined with Pivampicillin.Approved, Investigational, Vet Approved
ApramycinThe serum concentration of Apramycin can be decreased when it is combined with Pivampicillin.Experimental, Vet Approved
ArbekacinThe serum concentration of Arbekacin can be decreased when it is combined with Pivampicillin.Approved, Investigational
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Pivampicillin.Investigational
BekanamycinThe serum concentration of Bekanamycin can be decreased when it is combined with Pivampicillin.Experimental
ChlortetracyclineThe therapeutic efficacy of Pivampicillin can be decreased when used in combination with Chlortetracycline.Approved, Investigational, Vet Approved
ClorindionePivampicillin may increase the anticoagulant activities of Clorindione.Experimental
DemeclocyclineThe therapeutic efficacy of Pivampicillin can be decreased when used in combination with Demeclocycline.Approved
DibekacinThe serum concentration of Dibekacin can be decreased when it is combined with Pivampicillin.Experimental
DicoumarolPivampicillin may increase the anticoagulant activities of Dicoumarol.Approved
DihydrostreptomycinThe serum concentration of Dihydrostreptomycin can be decreased when it is combined with Pivampicillin.Investigational, Vet Approved
DiphenadionePivampicillin may increase the anticoagulant activities of Diphenadione.Experimental
DoxycyclineThe therapeutic efficacy of Pivampicillin can be decreased when used in combination with Doxycycline.Approved, Investigational, Vet Approved
Ethyl biscoumacetatePivampicillin may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
FluindionePivampicillin may increase the anticoagulant activities of Fluindione.Approved, Investigational
FramycetinThe serum concentration of Framycetin can be decreased when it is combined with Pivampicillin.Approved
GeneticinThe serum concentration of Geneticin can be decreased when it is combined with Pivampicillin.Experimental
GentamicinThe serum concentration of Gentamicin can be decreased when it is combined with Pivampicillin.Approved, Vet Approved
GENTAMICIN C1AThe serum concentration of GENTAMICIN C1A can be decreased when it is combined with Pivampicillin.Experimental
Hygromycin BThe serum concentration of Hygromycin B can be decreased when it is combined with Pivampicillin.Vet Approved
IsepamicinThe serum concentration of Isepamicin can be decreased when it is combined with Pivampicillin.Experimental
KanamycinThe serum concentration of Kanamycin can be decreased when it is combined with Pivampicillin.Approved, Investigational, Vet Approved
MedrogestoneThe serum concentration of Medrogestone can be decreased when it is combined with Pivampicillin.Approved
MethotrexateThe serum concentration of Methotrexate can be increased when it is combined with Pivampicillin.Approved
MicronomicinThe serum concentration of Micronomicin can be decreased when it is combined with Pivampicillin.Experimental
MinocyclineThe therapeutic efficacy of Pivampicillin can be decreased when used in combination with Minocycline.Approved, Investigational
Mycophenolic acidThe serum concentration of the active metabolites of Mycophenolic acid can be reduced when Mycophenolic acid is used in combination with Pivampicillin resulting in a loss in efficacy.Approved
NeamineThe serum concentration of Neamine can be decreased when it is combined with Pivampicillin.Experimental
NeomycinThe serum concentration of Neomycin can be decreased when it is combined with Pivampicillin.Approved, Vet Approved
NetilmicinThe serum concentration of Netilmicin can be decreased when it is combined with Pivampicillin.Approved, Investigational
OxytetracyclineThe therapeutic efficacy of Pivampicillin can be decreased when used in combination with Oxytetracycline.Approved, Investigational, Vet Approved
ParomomycinThe serum concentration of Paromomycin can be decreased when it is combined with Pivampicillin.Approved, Investigational
PhenindionePivampicillin may increase the anticoagulant activities of Phenindione.Approved, Investigational
PhenprocoumonPivampicillin may increase the anticoagulant activities of Phenprocoumon.Approved, Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Pivampicillin.Approved
PlazomicinThe serum concentration of Plazomicin can be decreased when it is combined with Pivampicillin.Investigational
ProbenecidThe serum concentration of Pivampicillin can be increased when it is combined with Probenecid.Approved, Investigational
PuromycinThe serum concentration of Puromycin can be decreased when it is combined with Pivampicillin.Experimental
RibostamycinThe serum concentration of Ribostamycin can be decreased when it is combined with Pivampicillin.Approved, Investigational
SisomicinThe serum concentration of Sisomicin can be decreased when it is combined with Pivampicillin.Investigational
StreptomycinThe serum concentration of Streptomycin can be decreased when it is combined with Pivampicillin.Approved, Vet Approved
TetracyclineThe therapeutic efficacy of Pivampicillin can be decreased when used in combination with Tetracycline.Approved, Vet Approved
TioclomarolPivampicillin may increase the anticoagulant activities of Tioclomarol.Experimental
TobramycinThe serum concentration of Tobramycin can be decreased when it is combined with Pivampicillin.Approved, Investigational
WarfarinPivampicillin may increase the anticoagulant activities of Warfarin.Approved
Food Interactions
  • Take without regard to meals.

References

General References
  1. Albertson TE, Louie S, Chan AL: The diagnosis and treatment of elderly patients with acute exacerbation of chronic obstructive pulmonary disease and chronic bronchitis. J Am Geriatr Soc. 2010 Mar;58(3):570-9. doi: 10.1111/j.1532-5415.2010.02741.x. [PubMed:20398122]
  2. Chanteux H, Van Bambeke F, Mingeot-Leclercq MP, Tulkens PM: Accumulation and oriented transport of ampicillin in Caco-2 cells from its pivaloyloxymethylester prodrug, pivampicillin. Antimicrob Agents Chemother. 2005 Apr;49(4):1279-88. [PubMed:15793098]
External Links
Human Metabolome Database
HMDB0015542
KEGG Compound
C11750
PubChem Compound
33478
PubChem Substance
46505340
ChemSpider
30899
ChEBI
8255
ChEMBL
CHEMBL3182343
Therapeutic Targets Database
DAP001171
PharmGKB
PA164776912
Wikipedia
Pivampicillin
ATC Codes
J01CR50 — Combinations of penicillinsJ01CA02 — Pivampicillin

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Powder, for solutionOral175 mg
TabletOral500 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0354 mg/mLALOGPS
logP1.43ALOGPS
logP2.07ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)11.71ChemAxon
pKa (Strongest Basic)7.44ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area128.03 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity116.25 m3·mol-1ChemAxon
Polarizability47.54 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9213
Blood Brain Barrier-0.9918
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.5543
P-glycoprotein inhibitor INon-inhibitor0.9052
P-glycoprotein inhibitor IINon-inhibitor0.9543
Renal organic cation transporterNon-inhibitor0.9423
CYP450 2C9 substrateNon-substrate0.8983
CYP450 2D6 substrateNon-substrate0.8513
CYP450 3A4 substrateNon-substrate0.5094
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorInhibitor0.796
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9283
Ames testNon AMES toxic0.8164
CarcinogenicityNon-carcinogens0.6461
BiodegradationNot ready biodegradable0.9769
Rat acute toxicity1.9193 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9996
hERG inhibition (predictor II)Non-inhibitor0.815
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as n-acyl-alpha amino acids and derivatives. These are compounds containing an alpha amino acid (or a derivative thereof) which bears an acyl group at its terminal nitrogen atom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
N-acyl-alpha amino acids and derivatives
Alternative Parents
Alpha amino acid esters / Penams / Acylals / Aralkylamines / Benzene and substituted derivatives / Dicarboxylic acids and derivatives / Tertiary carboxylic acid amides / Thiazolidines / Azetidines / Thiohemiaminal derivatives
show 10 more
Substituents
Alpha-amino acid ester / N-acyl-alpha amino acid or derivatives / Penam / Acylal / Aralkylamine / Monocyclic benzene moiety / Dicarboxylic acid or derivatives / Benzenoid / Beta-lactam / Tertiary carboxylic acid amide
show 27 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
penicillanic acid ester (CHEBI:8255)

Targets

Kind
Protein
Organism
Clostridium perfringens (strain 13 / Type A)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transferase activity, transferring glycosyl groups
Specific Function
Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan str...
Gene Name
pbpA
Uniprot ID
Q8XJ01
Uniprot Name
Penicillin-binding protein 1A
Molecular Weight
75176.35 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Okamoto T, Yoshiyama H, Nakazawa T, Park ID, Chang MW, Yanai H, Okita K, Shirai M: A change in PBP1 is involved in amoxicillin resistance of clinical isolates of Helicobacter pylori. J Antimicrob Chemother. 2002 Dec;50(6):849-56. [PubMed:12461003]

Drug created on August 29, 2007 12:48 / Updated on June 02, 2018 06:51