Selective Role of Sulfotransferase 2A1 (SULT2A1) in the N-Sulfoconjugation of Quinolone Drugs in Humans

Senggunprai, Laddawan; Yoshinari, Kouichi; Yamazoe, Yasushi

doi:10.1124/dmd.109.027441

Cited by 39 publications

(32 citation statements)

References 27 publications

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“…SULT2A1 is also termed as dehydroepiandrosterone sulfotransferase (DHEA ST) and conjugates various hydroxysteroids such as DHEA, androgens, bile acids and oestrone (Comer et al, 1993). Recently, a role of SULT2A1 in metabolism of quinolone drugs in humans was confirmed (Senggunprai et al, 2009). Clinically relevant substrates for other cytosolic sulfotransferases have not been identified yet.…”

Section: Substrates Of Sultsmentioning

confidence: 99%

Phase II Drug Metabolism

Jančová¹,

Siller²

2012

Topics on Drug Metabolism

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Section: Substrates Of Sultsmentioning

confidence: 99%

Phase II Drug Metabolism

Jančová¹,

Siller²

2012

Topics on Drug Metabolism

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“…Nevertheless, N-sulfation is a crucial reaction in the modification of carbohydrate chains in macromolecules such as heparin and heparan sulfate, common components of proteoglycan 44 . N-Sulfoconjugation is also involved in the metabolism of xenobiotics such as quinolones and amino drugs 45 . The PAPS is a universal sulfate (or, correctly sulfonate) donor molecule required for all sulfonation reactions and shown that it can be synthesized by all tissues in mammals 46 .…”

Section: Interspecies Differences In Ugt Enzymesmentioning

confidence: 99%

Phase Ii Drug Metabolizing Enzymes

Jančová¹,

Anzenbacher²,

Anzenbacherová³

2010

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

477

347

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“…Like rifapentine, moxifloxacin has a long half-life (9 to 12 h) (8,18), making it an attractive companion drug to prevent selection of rifapentine-resistant strains when the drugs are administered intermittently. However, moxifloxacin is a substrate of p glycoprotein (6), sulfotransferases (17), and glucuronosyltransferases (19), which may be induced by rifapentine, thus reducing systemic concentrations of moxifloxacin.…”

mentioning

confidence: 99%

Moxifloxacin Population Pharmacokinetics in Patients with Pulmonary Tuberculosis and the Effect of Intermittent High-Dose Rifapentine

Zvada¹,

Denti²,

Geldenhuys³

et al. 2012

Antimicrob Agents Chemother

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dWe described the population pharmacokinetics of moxifloxacin and the effect of high-dose intermittent rifapentine in patients with pulmonary tuberculosis who were randomized to a continuation-phase regimen of 400 mg moxifloxacin and 900 mg rifapentine twice weekly or 400 mg moxifloxacin and 1,200 mg rifapentine once weekly. A two-compartment model with transit absorption best described moxifloxacin pharmacokinetics. Although rifapentine increased the clearance of moxifloxacin by 8% during antituberculosis treatment compared to that after treatment completion without rifapentine, it did not result in a clinically significant change in moxifloxacin exposure. The duration of standard therapy for pulmonary tuberculosis is at least 6 months, and direct observation of treatment doses is promoted to support treatment adherence. Strategies aiming to shorten the duration of treatment or reduce the frequency of treatment doses are desirable. Rifapentine has a long half-life (7) and has superior in vitro activity against Mycobacterium tuberculosis compared to rifampin (9). Moxifloxacin has demonstrated potent bactericidal and sterilizing activity against M. tuberculosis in vitro and in mouse models (11,12). Like rifapentine, moxifloxacin has a long half-life (9 to 12 h) (8, 18), making it an attractive companion drug to prevent selection of rifapentine-resistant strains when the drugs are administered intermittently. However, moxifloxacin is a substrate of p glycoprotein (6), sulfotransferases (17), and glucuronosyltransferases (19), which may be induced by rifapentine, thus reducing systemic concentrations of moxifloxacin.To investigate the effects of rifapentine on moxifloxacin pharmacokinetics, we enrolled 28 adults diagnosed with pulmonary tuberculosis who were participating in the RIFAQUIN study (ISRCTN 44153044; http://ipc.nxgenomics.org/intertb /download/RIFAQUIN_Protocol_v_1.8_15_April_2011_FINAL .pdf) at the study site in Worcester, South Africa. Separate written informed consent for the pharmacokinetic study was obtained from RIFAQUIN study participants who were randomized to the two investigational arms with continuation-phase regimens of 1,200 mg rifapentine and 400 mg moxifloxacin once weekly or 900 mg rifapentine and 400 mg moxifloxacin twice weekly. The study protocol was reviewed and approved by the Research Ethics Committee of the University of Cape Town and the Medicines Control Council of South Africa.Plasma concentration data were collected during coadministration of moxifloxacin and rifapentine in the fourth month of tuberculosis treatment and again after a single 400-mg moxifloxacin dose 4 to 8 weeks after completion of tuberculosis treatment. At each occasion, blood samples were collected immediately before and at 1,3,5,7,10,12, 26, and 50 h after the dose.Plasma moxifloxacin concentrations were determined using a validated liquid chromatography-tandem mass spectrometry assay method developed in the Division of Clinical Pharmacology, University of Cape Town. The samples were processed with a protein...

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Selective Role of Sulfotransferase 2A1 (SULT2A1) in the N-Sulfoconjugation of Quinolone Drugs in Humans

Cited by 39 publications

References 27 publications

Phase II Drug Metabolism

Phase II Drug Metabolism

Phase Ii Drug Metabolizing Enzymes

Moxifloxacin Population Pharmacokinetics in Patients with Pulmonary Tuberculosis and the Effect of Intermittent High-Dose Rifapentine

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