Doripenem
Encyclopedia
Doripenem is an ultra-broad spectrum injectable antibiotic
. It is a beta-lactam
and belongs to the subgroup of carbapenem
s. It was launched by Shionogi Co. of Japan under the brand name Finibax in 2005 and is being marketed outside Japan by Johnson & Johnson
. It is particularly active against Pseudomonas aeruginosa
.
Doripenem can be used for bacterial infections such as: complex abdominal infections, pneumonia within the setting of a hospital, and complicated infections of the urinary tract including kidney infections with septicemia. Primarily, doripenem decreases the process of cell wall growth, which eventually leads to elimination of the infectious cell bacteria altogether.
It is recommended that those allergic to doripenem or to any type of beta-lactam antibiotics such as cephalosporin or other Carbapenems not receive doripenem.
Doripenem was approved by the United States Food and Drug Administration
on October 12, 2007, to be sold under the tradename Doribax.
Beta-lactamases (such as penicillinases) formed by gram-positive and gram-negative bacteria can stabilize doripenem to hydrolysis. However, carbapenem hydrolyzing beta-lactamases are an exception.
On average, about 8.1% of plasma proteins attached to doripenem; it is separate from drug concentrations of plasma. Doripenem’s distribution volume is close to that of extracellular fluid volume in humans (18.2 L). When doripenem is essentially stable the average volume of distribution is approximately 16.8 L. Within the few of the body’s fluids and tissues, Doripenem is filtered successfully as well as reach concentration levels that are able to restrain from more vulnerable bacteria than what is required.
Metabolism
Doripenem is metabolized by the enzyme dehydropeptidase-I into an inactive ring-opened metabolite.
Excretion
In young and healthy adults, the elimination half-life of doripenem considering the average plasma terminal is normally around 1 hour. The plasma clearance is about 15.9L/hour and the average renal clearance is 10.3 L/hour. Research indicates doripenem is filtered by the glomerular capillary bed in Bowman’s capsule and the tubular secretions in the nephron.
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
. It is a beta-lactam
Beta-lactam antibiotic
β-Lactam antibiotics are a broad class of antibiotics, consisting of all antibiotic agents that contains a β-lactam nucleus in its molecular structure. This includes penicillin derivatives , cephalosporins , monobactams, and carbapenems...
and belongs to the subgroup of carbapenem
Carbapenem
Carbapenems are a class of β-lactam antibiotics with a broad spectrum of antibacterial activity. They have a structure that renders them highly resistant to most β-lactamases...
s. It was launched by Shionogi Co. of Japan under the brand name Finibax in 2005 and is being marketed outside Japan by Johnson & Johnson
Johnson & Johnson
Johnson & Johnson is an American multinational pharmaceutical, medical devices and consumer packaged goods manufacturer founded in 1886. Its common stock is a component of the Dow Jones Industrial Average and the company is listed among the Fortune 500....
. It is particularly active against Pseudomonas aeruginosa
Pseudomonas aeruginosa
Pseudomonas aeruginosa is a common bacterium that can cause disease in animals, including humans. It is found in soil, water, skin flora, and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also in hypoxic atmospheres, and has, thus, colonized many...
.
Doripenem can be used for bacterial infections such as: complex abdominal infections, pneumonia within the setting of a hospital, and complicated infections of the urinary tract including kidney infections with septicemia. Primarily, doripenem decreases the process of cell wall growth, which eventually leads to elimination of the infectious cell bacteria altogether.
It is recommended that those allergic to doripenem or to any type of beta-lactam antibiotics such as cephalosporin or other Carbapenems not receive doripenem.
Doripenem was approved by the United States Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
on October 12, 2007, to be sold under the tradename Doribax.
Chemistry and Pharmacology
Doripenem is a beta-lactam antibiotic agent belonging to the carbapenem group, with a broad spectrum of bacterial sensitivity. Although doripenem may be quite similar to other related carbapenem agents, the antibiotic includes several divergent properties. For example, doripenem includes a transfiguration of hydroxyethyl group, and in position 1 there is a carbon atom. These differences make the agent more stable against other pathogens. Doripenem inhibits renal dehydropeptidase-1 hydrolysis due to its structure containing a single side chain, 1-beta methyl. Additionally, within the molecular structure a sulfamoylaminomethyl-pyrrolindinylthio group is attached to a side chain giving the molecule increased antibacterial action against gram-negative microbes. In vivo, doripenem inhibits the synthesis of cell walls by attaching itself to penicillin binding proteins, also known as PBPs.Physicochemical Properties
Doripenem appears as crystalline powder anywhere from a white to somewhat yellowish colour.Doripenem is moderately soluble in water, slightly soluble in methanol, and virtually insoluble in ethanol. Doripenem is also solution in N,N-dimethylformamide. Doripenem is composed of a 6 asymmetrical carbon molecule and is most commonly displayed by one pure isomer. In terms of doripenem for injection, the crystallized powered drug can form a monohydrate when mixed with water. However, Doripenem has not been proven to possess polymorphism.Resistance
Potential avenues for the development of resistance to doripenem are: altered PBPs (penicillin binding protein), activity in the permeability of the outer membrane being reduced especially when accepting foreign toxic substances within the cell, and hydrolyzing enzymes from the carbapenem deactivating the drug from functioning.Beta-lactamases (such as penicillinases) formed by gram-positive and gram-negative bacteria can stabilize doripenem to hydrolysis. However, carbapenem hydrolyzing beta-lactamases are an exception.
Pharmacokinetics
DistributionOn average, about 8.1% of plasma proteins attached to doripenem; it is separate from drug concentrations of plasma. Doripenem’s distribution volume is close to that of extracellular fluid volume in humans (18.2 L). When doripenem is essentially stable the average volume of distribution is approximately 16.8 L. Within the few of the body’s fluids and tissues, Doripenem is filtered successfully as well as reach concentration levels that are able to restrain from more vulnerable bacteria than what is required.
Metabolism
Doripenem is metabolized by the enzyme dehydropeptidase-I into an inactive ring-opened metabolite.
Excretion
In young and healthy adults, the elimination half-life of doripenem considering the average plasma terminal is normally around 1 hour. The plasma clearance is about 15.9L/hour and the average renal clearance is 10.3 L/hour. Research indicates doripenem is filtered by the glomerular capillary bed in Bowman’s capsule and the tubular secretions in the nephron.