Active renal secretion of NXY-059, a novel neuroprotectant, is mediated via an organic acid transporter

Journal of Clinical Pharmacology

Volumn 47, Issue 7, 2007, Pages 909-914

  Cheng, Yi Fang ^c   Strid, Stig ^c   Borgâ, Olof ^a   Nilsson, Dag ^c   Werner, Johan ^b  

^a Borgå PK Consulting ^*  (Sweden)

^b Xendo Drug Development Services   (Netherlands)

^c ASTRAZENECA R AND D   (Sweden)

Author keywords

Neuroprotectant; NXY 059; Pharmacokinetics; Renal secretion; Transporter

Indexed keywords

CARRIER PROTEIN; CIMETIDINE; DISUFENTON SODIUM; INULIN; ORGANIC ACID TRANSPORTER; PROBENECID; UNCLASSIFIED DRUG; BENZENESULFONIC ACID DERIVATIVE; DIAGNOSTIC AGENT; NEUROPROTECTIVE AGENT; ORGANIC ANION TRANSPORTER;

ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANEMIA; AREA UNDER THE CURVE; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG EXCRETION; DRUG SAFETY; DRUG URINE LEVEL; EYE PAIN; FEMALE; GLOMERULUS FILTRATION RATE; HEADACHE; HUMAN; HUMAN EXPERIMENT; LACTATE DEHYDROGENASE BLOOD LEVEL; MALE; NEUROPROTECTION; NORMAL HUMAN; SIDE EFFECT; URINARY EXCRETION; BLOOD; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; DRUG ANTAGONISM; DRUG INTERACTION; KIDNEY FUNCTION TEST; MIDDLE AGED; PHYSIOLOGY; RANDOMIZED CONTROLLED TRIAL; URINE;

ADULT; BENZENESULFONATES; CIMETIDINE; DRUG INTERACTIONS; FEMALE; GLOMERULAR FILTRATION RATE; HUMANS; INULIN; KIDNEY FUNCTION TESTS; MALE; MIDDLE AGED; NEUROPROTECTIVE AGENTS; ORGANIC ANION TRANSPORTERS; PROBENECID;

EID: 34548033023     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1177/0091270007301803     Document Type: Article

References (11)

1. Edenius C, Strid S, Borgå O, Breitholtz-Emanuelsson A, Vallen KL, Fransson B. Pharmacokinetics of NXY-059, a nitrone-based free radical trapping agent, in healthy young and elderly subjects. J Stroke Cerebrovasc Dis. 2002;11:34-43.
2. Strid S, Borgå O, Edenius C, Jostell KG, Odergren T, Weil A. Pharmacokinetics in renally impaired subjects of NXY-059, a nitrone-based, free-radical trapping agent developed for the treatment of acute stroke. Eur J Clin Pharmacol. 2002;58:409-415.
3. Shitara Y, Sato H, Sugiyama Y. Evaluation of drug-drug interaction in the hepatobiliary and renal transport of drugs. Annu Rev Pharmacol Toxicol. 2005;45:689-723. (Pubitemid 40261822)
4. Pietig G, Mehrens T, Hirsch JR, Centinkaya I, Piechota H, Schlatter E. Properties and regulation of organic cation transport in freshly isolated human proximal tubules. J Biol Chem. 2001;276: 33741-33746.
5. Prince M. Comparison of creatinine clearance to inulin clearance in the determination of glomerular filtration rate. J Urol. 1972; 107:559.
6. Bojesen H. Method for the determination of inulin in plasma. Acta Med Scand. 1952;142:275.
7. ShigaT,HashiguchiM,UraeA,KasanukiH,RikihisaT. EffectofCimetidineandprobenecidonpilsicainiderenalclearanceinhumans. ClinPharmacolTher.2000;67:222-228.(Pubitemid30176379)
8. ArvidssonA,BorgåO,KagerL,PieperR. Renaleliminationofcefoxitinandeffectofprobenecidaftersingleandrepeateddoses. JAntimicrobChemother.1981;7:423-430.(Pubitemid11124297)
9. Borgå O, Larsson R, Lunell E. Effects of probenecid on enprofylline kinetics in man. Eur J Clin Pharmacol. 1986;30:221-223. (Pubitemid 16166074)
10. Emanuelsson BM, Beermann B, Paalzow LK. Non-linear elimination and protein binding of probenecid. Eur J Clin Pharmacol. 1987;32:395-401. (Pubitemid 17077188)
11. Wemer J, Cheng Y-F, Nilsson D, et al. Safety, tolerability and pharmacokinetics of escalating doses of NXY-059 in healthy young and elderly subjects. Curr Med Res Opin. 2006;22:1813-1823. (Pubitemid 44449238)