Doripenem Physical and chemical properties

Doripenem (Doribax, Finibax) is a carbapenem antibiotic drug.It is a beta-lactam antibiotic drug that kills Pseudomonas aeruginosa.

Doripenem is indicated for bacterial infections such as: complicated abdominal infections, pneumonia in a hospital setting, and complicated infections of the urinary tract, including kidney infections with sepsis.Compared with earlier members of the carbapenem class, doripenem is more stable in aqueous solution, so it can be given as an infusion over a period of 4 hours or longer, which may be beneficial in the treatment of some difficult-to-treat diseases. Infect.It may have a lower risk of inducing seizures than other carbapenems.

Chemistry and pharmacology 

Doripenem is a β-lactam antibiotic belonging to the carbapenem class with broad-spectrum sensitivity to bacteria including Gram-positive and Gram-negative bacteria.In vivo, doripenem inhibits cell wall synthesis by attaching itself to penicillin-binding protein (also known as PBP).However, it is not active against MRSA. It is stable to beta-lactamases (including broad-spectrum enzymes), but sensitive to the action of carbapenemases.Doripenem was also more effective against Pseudomonas aeruginosa than other carbapenems.

Physical and chemical properties

Doripenem appears as a crystalline powder that varies in color from white to pale yellow.Doripenem is slightly soluble in water,slightly soluble in methanol, and practically insoluble in ethanol.Doripenem is also soluble in N,N-dimethylformamide.The chemical configuration of doripenem has 6 asymmetric carbon atoms (6 stereocenters) and is most commonly provided as a pure isomer.In the case of doripenem for injection, the crystalline powdered drug forms a monohydrate when mixed with water.However, doripenem has not been shown to be polymorphic

Side effects

Seizure risk: Carbapenems have been reported to commonly cause seizures in some people. Additionally, those who already have epilepsy may be at risk of further seizures if they use valproic acid for seizure control; doripenem has been found to reduce serum concentrations of valproic acid.Infection-related: Clostridium difficile infection has been associated with doripenem use also noted that it increases mortality in patients with ventilator-associated bacterial pneumonia and is therefore no longer recommended as a treatment for this disease.

Resistance

Potential pathways for the development of resistance to doripenem are: changes in PBP (penicillin-binding protein), decreased outer membrane permeability activity, especially in the intracellular reception of foreign toxic substances, and drug degradation by carbapenem hydrolases Inactivation. Beta-lactamases (such as penicillinase) formed by Gram-positive and Gram-negative bacteria can stabilize the hydrolysis of doripenem.However, β-lactamases that hydrolyze carbapenems are an exception.

Pharmacokinetics

Distribution

On average, about 8.1% of plasma proteins were attached to doripenem; it was separated from the drug concentration in plasma.The distribution volume of doripenem is close to the human extracellular fluid volume (18.2 L).When doripenem is substantially stable, the mean volume of distribution is approximately 16.8 L. In a small number of bodily fluids and tissues, doripenem was successfully filtered to a concentration level capable of inhibiting more fragile bacteria than needed.

Metabolism

Doripenem is metabolized by dehydropeptidase-I to inactive ring-opened metabolites.

Excretion

In young healthy adults, the elimination half-life of doripenem is typically approximately 1 hour, taking into account the mean plasma terminal phase.Plasma clearance was approximately 15.9 L/hour and mean renal clearance was 10.3 L/hour. Studies have shown that doripenem is filtered by glomerular capillary beds in Bowman’s capsule and by tubular secretions in nephrons.

Regulation and marketing

It was launched under the brand name by Shionogi Co. in Japan in 2005 and sold outside of Japan by Johnson & Johnson.Doripenem was approved by the U.S. Food and Drug Administration on October 12, 2007, and is marketed under the trade name Doribax.It is the fourth member of the carbapenem class to be approved.