Doripenem (Doribax, Finibax) is an antibiotic drug in the

carbapenem Carbapenems are a class of very effective antibiotic agents most commonly used for the treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multidrug-resistant (MDR) bacterial infections. ...

class. It is a

beta-lactam A beta-lactam (β-lactam) ring is a four-membered lactam. A ''lactam'' is a cyclic amide, and ''beta''-lactams are named so because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl. The simplest β-lactam possible i ...

antibiotic drug able to kill ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. aerug ...

''. 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

sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

. The greater stability of doripenem in aqueous solution compared to earlier members of the carbapenem class allows it to be administered as an infusion over 4 hours or more, which may be advantageous in the treatment of certain difficult-to-treat infections. It may present a lower risk of inducing seizures than other carbapenems.

Chemistry and pharmacology

Doripenem is a beta-lactam antibiotic agent belonging to the carbapenem group, with a broad spectrum of bacterial sensitivity including both

gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...

and

gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...

bacteria. In vivo, doripenem inhibits the synthesis of cell walls by attaching itself to penicillin-binding proteins, also known as PBPs. However it is not active against

MRSA Methicillin-resistant ''Staphylococcus aureus'' (MRSA) is a group of Gram-positive bacteria that are genetically distinct from other strains of ''Staphylococcus aureus''. MRSA is responsible for several difficult-to-treat infections in humans. ...

. It is stable against

beta-lactamases Beta-lactamases, (β-lactamases) are enzymes () produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems ( ertapenem), although carbapenems ...

including those with extended spectrum, but it is susceptible to the action of

carbapenemase Beta-lactamases, (β-lactamases) are enzymes () produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems ( ertapenem), although carbapenems ...

s. Doripenem is also more active against

than other carbapenems.

Physicochemical properties

Doripenem appears as crystalline powder, with colour anywhere from a white to somewhat yellowish. Doripenem is moderately soluble in water, slightly soluble in methanol, and virtually insoluble in ethanol. Doripenem is also soluble in N,N-dimethylformamide. Doripenem's chemical configuration has 6 asymmetrical carbon atoms (6 stereocentres) and is most commonly supplied as one pure isomer. In terms of doripenem for injection, the crystallized powdered drug can form a monohydrate when mixed with water. However, doripenem has not been proven to possess polymorphism

Adverse effects

*Seizure risk: carbapenems in general have been reported to cause seizure activity in some people. In addition, those who already have a seizure disorder may be at risk for further seizures if they are using valproic acid to control their seizures; doripenem has been found to decrease serum concentrations of valproic acid. *Infection related: use of doripenem can lead to clostridium difficile infection. It has also been noted to increase mortality in people who have ventilator-associated bacterial pneumonia, and is no longer recommended as a treatment for this condition.

Resistance

Potential avenues for the development of resistance to doripenem are: altered PBPs (penicillin-binding protein), reduced activity in the permeability of the outer membrane especially when accepting foreign toxic substances within the cell, and deactivation of the drug by hydrolyzing enzymes from the carbapenem. Beta-lactamases (such as penicillinases) formed by

and gram-negative bacteria can stabilize doripenem to hydrolysis. However, carbapenem-hydrolyzing beta-lactamases are an exception.

Pharmacokinetics

Distribution

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 reaching 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 15.9 L/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.

Regulatory and marketing

It was launched by Shionogi Co. of Japan under the

brand name A brand is a name, term, design, symbol or any other feature that distinguishes one seller's good or service from those of other sellers. Brands are used in business, marketing, and advertising for recognition and, importantly, to create an ...

in 2005 and is being marketed outside Japan by Johnson & Johnson. Doripenem was approved by the United States

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

on October 12, 2007, to be sold under the tradename Doribax. It is the fourth member of the carbapenem class to be approved in the United States.