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a uricosuric drug that reduces the level of uric acid in the blood; used to treat gout

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/04/12 16:36:25」(JST)

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Probenecid (Lannett's Probalan) is a uricosuric drug that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia.

Probenecid was developed as an alternative to caronamide^[1] to competitively inhibit renal excretion of some drugs, thereby increasing their plasma concentration and prolonging their effects.

Uses

Probenecid is primarily used to treat gout and hyperuricemia.

During World War II, probenecid was used to extend limited supplies of penicillin,^[2] and is still used to increase antibiotic concentrations in serious infections. In one study, probenecid was shown to more than double blood concentrations of oseltamivir (trade name Tamiflu), an antiviral drug used to combat the flu, suggesting this property applies to antivirals, as well.^[3]

It has also found use as a masking agent.^[4]

Drug interactions

Some of the important clinical interactions of probenecid include those with captopril, indomethacin, ketoprofen, ketorolac, naproxen, cephalosporins, quinolones, penicillins, methotrexate, zidovudine, ganciclovir, lorazepam and acyclovir. In all these interactions, the excretion of these drugs is reduced due to probenecid.

Pharmacology

In the kidneys, probenecid is filtered at the glomerulus, secreted in the proximal tubule and reabsorbed in the distal tubule.

Probenecid works by interfering with the kidneys' organic anion transporter (OAT), which reclaims uric acid from the urine and returns it to the plasma.^[5] If probenecid (an organic acid) is present, the OAT binds preferentially to it (instead of to uric acid), preventing reabsorption of the uric acid. Hence, the urine retains more uric acid, lowering uric acid concentration in the plasma. (This is a good example of a medical usage for competition between substrates transported across cell membranes).

References

^ MASON RM (June 1954). "Studies on the Effect of Probenecid ('Benemid') in Gout". Ann. Rheum. Dis. 13 (2): 120–30. doi:10.1136/ard.13.2.120. PMC 1030399. PMID 13171805.
^ Butler D (2005). "Wartime tactic doubles power of scarce bird-flu drug". Nature 438 (7064): 6. doi:10.1038/438006a. PMID 16267514.
^ Hill G, Cihlar T, Oo C et al. (2002). "The anti-influenza drug oseltamivir exhibits low potential to induce pharmacokinetic drug interactions via renal secretion-correlation of in vivo and in vitro studies". Drug Metab. Dispos. 30 (1): 13–9. doi:10.1124/dmd.30.1.13. PMID 11744606.
^ Morra V, Davit P, Capra P, Vincenti M, Di Stilo A, Botrè F (December 2006). "Fast gas chromatographic/mass spectrometric determination of diuretics and masking agents in human urine: Development and validation of a productive screening protocol for antidoping analysis". J Chromatogr A 1135 (2): 219–29. doi:10.1016/j.chroma.2006.09.034. PMID 17027009.
^ Hsyu PH, Gisclon LG, Hui AC, Giacomini KM (January 1988). "Interactions of organic anions with the organic cation transporter in renal BBMV". Am. J. Physiol. 254 (1 Pt 2): F56–61. PMID 2962517.

UpToDate Contents

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1. 痛風再発の予防 prevention of recurrent gout
2. HIV感染患者における薬剤抵抗性性器単純ヘルペスウイルス感染の治療 treatment of drug resistant genital herpes simplex virus infection in hiv infected patients
3. 危険を伴う中絶 unsafe abortion
4. 尿酸のバランス uric acid balance
5. 神経梅毒 neurosyphilis

English Journal

Fuzzy optimization for detecting enzyme targets of human uric acid metabolism.

Hsu KC, Wang FS.SourceDepartment of Chemical Engineering, National Chung Cheng University, Chiayi 62102, Taiwan.
Bioinformatics (Oxford, England).Bioinformatics.2013 Dec 15;29(24):3191-8. doi: 10.1093/bioinformatics/btt564. Epub 2013 Sep 26.
MOTIVATION: Mathematical modeling and optimization have been used for detecting enzyme targets in human metabolic disorders. Such optimal drug design methods are generally differentiated as two stages, identification and decision-making, to find optimal targets. We developed a unified method named f
PMID 24078686

Utilization patterns of Antihyperuricemic Agents Following Safety Announcement on Allopurinol and Benzbromarone by Taiwan Food and Drug Administration.

Cheng CL, Chao PH, Hsu JC, Weng MM, On AW, Yang YH.SourceInstitute of Clinical Pharmacy and Pharmaceutical Science, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Pharmacoepidemiology and drug safety.Pharmacoepidemiol Drug Saf.2013 Dec 5. doi: 10.1002/pds.3550. [Epub ahead of print]
OBJECTIVE: The purpose of this study is to evaluate the utilization of four approved antihyperuricemic agents in Taiwan before and after two safety announcements rescinded an indication for allopurinol and added a warning on benzbromarone-induced hepatotoxicity in the year 2005.METHODS: An interrupt
PMID 24307655

Impact of lipopolysaccharide-induced inflammation on the disposition of the aminocephalosporin cefadroxil.

Huh Y, Keep RF, Smith DE.SourceDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA.
Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2013 Dec;57(12):6171-8. doi: 10.1128/AAC.01497-13. Epub 2013 Sep 30.
The purpose of this study was to determine if the disposition of cefadroxil, an α-amino-containing β-lactam antibiotic, changes during lipopolysaccharide (LPS)-induced acute inflammation. Six hours after LPS or saline treatment, mice received 1 nmol/g cefadroxil intravenously along with inulin for
PMID 24080658

Japanese Journal

A simple method to evaluate reactivity of acylglucuronides optimized for early stage drug discovery

Jinno Norimasa,Ohashi Shigeki,Tagashira Mizuka,Kohira Terutomo,Yamada Shizuo
Biological and Pharmaceutical Bulletin, 2013
… We evaluated the half-lives of 10 drugs: 3 safe drugs (telmisartan, gemfibrozil and flufenamic acid) and 7 withdrawn or warning drugs (zomepirac, diclofenac, furosemide, ibuprofen, S-naproxen, probenecid and tolmetin). …
NAID 130003361534

Ribosomal protein L3 mediated the transport of digoxin in Xenopus laevis oocyte

Kobayashi Yasuna,Kawakami Kanako,Ohbayashi Masayuki [他],KOHYAMA Noriko,YAMAMOTO Toshinori
Journal of toxicological sciences 35(6), 827-834, 2010-12-01
… The maximum velocity of the transport of [3H]digoxin via RPL3 produced at physiological pH. However, we did not observe RPL3-mediated transport of several organic solutes such as [14C]androstenedione, [3H]dexamethasone, [3H]dehydroepiandrosterone sulfate, [3H]L-tryptophan, [14C]L-ascorbic acid, [14C]α-ketoglutarate, [14C]glutarate, [3H]methotrexate, [3H]bumetanide, [3H]probenecid, [14C]salicylic acid, [14C]theophylline and [3H]valproate. …
NAID 10026962974

Interactions of Human Organic Anion Transporters With Aristolochic Acids

Babu Ellappan,Takeda Michio,Nishida Ritsuo [他],Noshiro-Kofuji Rie,Yoshida Masaaki,Ueda Shiro,Fukutomi Toshiyuki,Anzai Naohiko,Endou Hitoshi
Journal of Pharmacological Sciences 113(2), 192-196, 2010
… Treatment of hOAT3 with AA-I resulted in a significant reduction in viability compared with that of mock, which was rescued by the organic anion transport inhibitor probenecid. …
NAID 130000251925

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★リンクテーブル★

リンク元	「薬理学」「痛風治療薬」「プロベネシド」

「薬理学」

Probenecid
Systematic (IUPAC) name
	4-(dipropylsulfamoyl)benzoic acid
Clinical data
Trade names	Probalan
AHFS/Drugs.com	monograph
MedlinePlus	a682395
Legal status	?
Routes	oral
Pharmacokinetic data
Protein binding	75-95%
Half-life	2-6 hours (dose: 0.5-1 g)
Excretion	renal (77-88%)
Identifiers
CAS number	57-66-9
ATC code	M04AB01
PubChem	CID 4911
IUPHAR ligand	4357
DrugBank	DB01032
ChemSpider	4742
UNII	PO572Z7917
KEGG	D00475
ChEMBL	CHEMBL897
Chemical data
Formula	C13H19NO4S
Mol. mass	285.36 g/mol
	SMILES O=S(=O)(N(CCC)CCC)c1ccc(C(=O)O)cc1;
	InChI InChI=1S/C13H19NO4S/c1-3-9-14(10-4-2)19(17,18)12-7-5-11(6-8-12)13(15)16/h5-8H,3-4,9-10H2,1-2H3,(H,15,16) ; Key:DBABZHXKTCFAPX-UHFFFAOYSA-N ;
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英: pharmacology
関: drug entries

定義

生物系と化学物質の選択的な相互作用を研究する学問 (SPC.2)

生物系と薬の相互作用

薬の生物系に対する相互作用：薬理作用 <-化学の視点
生物系の薬に対する相互作用：薬物動態 <-生物の視点

薬品の命名

Ending of the drug name	Category	Example
～afil	Erectile dysfunction	sildenafil
～ane	Inhalatinal general anesthetic	halothane
～azepam	Benzodiaizepine	diazepam
～azine	Phenothiazine (neuroleptic, antiemetic)	chlorpromazine
～azole	Ailtifungal	ketoconazole
～barbital	Barbiturate	phenobarbital
～caine	Local anesthetic	lidocaine
～cillin	Penicillin	methicillin
～cycline	Antibiotic, protein syntlesis inhibitor	tetracycline
～ipramine	TCA	iimipramine
～navir	Protease inhibitor	saquinavir
～olol	β-antagonist	propranolol
～operidol	Butyrophenone ( neuroleptic )	haloperidol
～oxin	Cardiac glycoside ( inotropic agent )	digoxin
～phylline	Methylxanthine	theophylline
～pril	ACE inhibitor	captopril
～terol	β₂ agonist	albuterol
～tidine	H₂ antagonist	cimtidine
～triptyline	TCA	amitriptyline
～tropine	Pituitary hormone	somatotropine
～zosin	a₁ antagonist	prazosin