Doripenem: Difference between revisions

{{Short description|Antibiotic}}

| Watchedfields = changed

| verifiedrevid = 458286101

| IUPAC_name = (4''R'',5''S'',6''S'')-6-(1-Hydroxyethyl)-4-methyl-7-oxo-3-(((5''S'')-5-((sulfamoylamino)methyl)pyrrolidin-3-yl)thio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

| image = Doripenem.svg

| tradename = Finibax, Doribax

| licence_EU = yes

| pregnancy_category = B

| excretion =

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 148016-81-3

| UNII_Ref = {{fdacite|correct|FDA}}

| KEGG_Ref = {{keggcite|correct|kegg}}

| ChEMBL_Ref = {{ebicite|correct|EBI}}

'''Doripenem''' ('''Doribax''', '''Finibax''') is an antibiotic drug in the [[carbapenem]] class. It is a [[beta-lactam antibiotic|beta-lactam]] antibiotic drug able to kill ''[[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 [[sepsis]].

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.<ref>{{cite journal | vauthors = Mazzei T | title = The pharmacokinetics and pharmacodynamics of the carbapanemes: focus on doripenem | journal = Journal of Chemotherapy | volume = 22 | issue = 4 | pages = 219–25 | date = August 2010 | pmid = 20685624 | doi = 10.1179/joc.2010.22.4.219 | s2cid = 72019292 }}</ref><ref>{{cite journal | vauthors = Greer ND | title = Doripenem (Doribax): the newest addition to the carbapenems | journal = Proceedings | volume = 21 | issue = 3 | pages = 337–41 | date = July 2008 | pmid = 18628935 | pmc = 2446428 | doi = 10.1080/08998280.2008.11928422 }}</ref> It may present a lower risk of inducing seizures than other carbapenems.<ref>{{cite journal | vauthors = Zhanel GG, Ketter N, Rubinstein E, Friedland I, Redman R | title = Overview of seizure-inducing potential of doripenem | journal = Drug Safety | volume = 32 | issue = 9 | pages = 709–16 | year = 2009 | pmid = 19670912 | doi = 10.2165/00002018-200932090-00001 | s2cid = 25385572 }}</ref>

==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]] and [[gram-negative]] 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]]. It is stable against [[beta-lactamases]] including those with extended spectrum, but it is susceptible to the action of [[carbapenemase]]s. Doripenem is also more active against [[Pseudomonas aeruginosa]] than other carbapenems.<ref name=JJ/>

==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{{cn|date=March 2023}}

==Adverse effects==

*Seizure risk: carbapenems in general have been reported to cause seizure activity in some people.<ref name="accessdata.fda.gov">{{cite web | title = Highlights of Prescribing Information: DORIBAX (doripenem for injection) | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022106s012lbl.pdf | publisher = U.S. Food and Drug Administration }}</ref> 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.<ref name="accessdata.fda.gov"/>

*Infection related: use of doripenem can lead to clostridium difficile infection.<ref name="accessdata.fda.gov"/> 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.<ref name="accessdata.fda.gov"/>

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 [[Gram-positive bacteria|gram-positive]] and gram-negative bacteria can stabilize doripenem to hydrolysis. However, carbapenem-hydrolyzing beta-lactamases are an exception.{{cn|date=March 2023}}

===Distribution===

On average, about 8.1% of plasma proteins attached to doripenem; it is separate from drug concentrations of plasma.<ref name=JJ>{{cite press release | url = https://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4364b1-02-Johnson.pdf | title = Doripenem for Injection for the Treatment of Nosocomial Pneumonia | date = July 16, 2008 | access-date = 2010-05-19 | publisher = [[Johnson & Johnson]]}}</ref> 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.{{cn|date=March 2023}}

===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.{{cn|date=March 2023}}

===Regulatory and marketing===

It was launched by [[Shionogi Co.]] of Japan under the [[brand name]] in 2005 and is being marketed outside Japan by [[Johnson & Johnson]]. Doripenem was approved by the United States [[Food and Drug Administration]] on October 12, 2007, to be sold under the tradename '''Doribax'''.<ref>{{cite press release | url = https://www.fda.gov/bbs/topics/NEWS/2007/NEW01728.html | title = FDA Approves New Drug to Treat Complicated Urinary Tract and Intra-Abdominal Infections | date = October 17, 2007 | access-date = 2007-10-25 | publisher = U.S. [[Food and Drug Administration]]}}</ref> It has since been discontinued in the United States.

== References ==

{{reflist}}

== Further reading ==

{{refbegin}}

* {{cite journal | vauthors = Nishino Y, Kobayashi M, Shinno T, Izumi K, Yonezawa H, Masui Y, Takahira M | title = Practical large-scale synthesis of doripenem: A novel 1β-methylcarbapenem antibiotic. | journal = Organic Process Research & Development| date = November 2003 | volume = 7 | issue = 6 | pages = 846–50 | doi = 10.1021/op034088n}}

* {{cite web | work = European Medicines Agency | date = 2008 | title = CHMP Assessment Report for Doribax | url = https://www.ema.europa.eu/en/documents/assessment-report/doribax-epar-public-assessment-report_en.pdf }}

* {{cite journal | vauthors = Hagerman JK, Knechtel SA, Kiepser ME | title = Doripenem: A new extended-spectrum carbapenem antibiotic. | journal = Formulary | date = December 2007 | volume = 42 | issue = 12 | pages = 676–688 }}

{{refend}}

[[Category:Sulfamides]]

[[Category:Drugs developed by Johnson & Johnson]]