Probenecid, an organic anion transporter 1 and 3 inhibitor, increases plasma and brain exposure of N-acetylcysteine

References

• Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA. (2007). N-Acetylcysteine-a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol 7:355–9
   PubMed Web of Science ®Google Scholar
• Borgstrom L, Kagedal B, Paulsen O. (1986). Pharmacokinetics of n-acetylcysteine in man. Eur J Clin Pharmacol 31:217–22
   PubMed Web of Science ®Google Scholar
• Cotgreave IA. (1997). N-acetylcysteine: pharmacological considerations and experimental and clinical applications. Adv Pharmacol 38:205–27
   PubMedGoogle Scholar
• Dodd S, Dean O, Copolov DL, et al. (2008). N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility. Expert Opin Biol Ther 8:1955–62
   PubMed Web of Science ®Google Scholar
• Donovan MD, O'brien FE, Boylan GB, et al. (2015). The effect of organic anion transporter 3 inhibitor probenecid on bumetanide levels in the brain: an integrated in vivo microdialysis study in the rat. J Pharm Pharmacol 67:501–10
   PubMed Web of Science ®Google Scholar
• Erdman AR, Mangravite LM, Urban TJ, et al. (2006). The human organic anion transporter 3 (oat3; slc22a8): genetic variation and functional genomics. Am J Physiol Renal Physiol 290:F905–12
   PubMed Web of Science ®Google Scholar
• Erickson MA, Hansen K, Banks WA. (2012). Inflammation-induced dysfunction of the low-density lipoprotein receptor-related protein-1 at the blood-brain barrier: protection by the antioxidant n-acetylcysteine. Brain Behav Immun 26:1085–94
   PubMed Web of Science ®Google Scholar
• Farr SA, Poon HF, Dogrukol-Ak D, et al. (2003). The antioxidants alpha-lipoic acid and n-acetylcysteine reverse memory impairment and brain oxidative stress in aged samp8 mice. J Neurochem 84:1173–83
   PubMed Web of Science ®Google Scholar
• Giustarini D, Milzani A, Dalle-Donne I, et al. (2012). N-acetylcysteine ethyl ester (nacet): a novel lipophilic cell-permeable cysteine derivative with an unusual pharmacokinetic feature and remarkable antioxidant potential. Biochem Pharmacol 84:1522–33
   PubMed Web of Science ®Google Scholar
• Grandjean EM, Berthet P, Ruffmann R, Leuenberger P. (2000). Efficacy of oral long-term n-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials. Clin Ther 22:209–21
   PubMed Web of Science ®Google Scholar
• Harada D, Naito S, Kawauchi Y, et al. (2001). Determination of reduced, protein-unbound, and total concentrations of n-acetyl-l-cysteine and l-cysteine in rat plasma by postcolumn ligand substitution high-performance liquid chromatography. Anal Biochem 290:251–9
   PubMed Web of Science ®Google Scholar
• Hoffer ME, Balaban C, Slade MD, et al. (2013). Amelioration of acute sequelae of blast induced mild traumatic brain injury by n-acetyl cysteine: a double-blind, placebo controlled study. PLoS One 8:e54163
   PubMed Web of Science ®Google Scholar
• Hurst GA, Shaw PB, LeMaistre CA. (1967). Laboratory and clinical evaluation of the mucolytic properties of acetylcysteine. Am Rev Respir Dis 96:962–70
   PubMed Web of Science ®Google Scholar
• Kalvass JC, Polli JW, Bourdet DL, et al. (2013). Why clinical modulation of efflux transport at the human blood-brain barrier is unlikely: the ITC evidence-based position. Clin Pharmacol Ther 94:80–94
   PubMed Web of Science ®Google Scholar
• Kikuchi R, Kusuhara H, Sugiyama D, Sugiyama Y. (2003). Contribution of organic anion transporter 3 (slc22a8) to the elimination of p-aminohippuric acid and benzylpenicillin across the blood-brain barrier. J Pharmacol Exp Ther 306:51–8
   PubMed Web of Science ®Google Scholar
• Koh AS, Simmons-Willis TA, Pritchard JB, et al. (2002). Identification of a mechanism by which the methylmercury antidotes n-acetylcysteine and dimercaptopropanesulfonate enhance urinary metal excretion: transport by the renal organic anion transporter-1. Mol Pharmacol 62:921–6
   PubMed Web of Science ®Google Scholar
• Kusuhara H, Sugiyama Y. (2005). Active efflux across the blood-brain barrier: role of the solute carrier family. NeuroRx 2:73–85
   PubMedGoogle Scholar
• Laskin OL, de Miranda P, King DH, et al. (1982). Effects of probenecid on the pharmacokinetics and elimination of acyclovir in humans. Antimicrob Agents Chemother 21:804–7
   PubMed Web of Science ®Google Scholar
• Löscher W, Potschka H. (2005). Role of drug efflux transporters in the brain for drug disposition and treatment of brain diseases. Progress in Neurobiology 76:22–76
   PubMed Web of Science ®Google Scholar
• Maeda K, Tian Y, Fujita T, et al. (2014). Inhibitory effects of p-aminohippurate and probenecid on the renal clearance of adefovir and benzylpenicillin as probe drugs for organic anion transporter (oat) 1 and oat3 in humans. Eur J Pharm Sci 59:94–103
   PubMed Web of Science ®Google Scholar
• Margulies S, Anderson G, Atif F, et al. (2016). Combination therapies for traumatic brain injury: retrospective considerations. J Neurotrauma 33:101–12
   PubMed Web of Science ®Google Scholar
• McLellan LI, Lewis AD, Hall DJ, et al. (1995). Uptake and distribution of n-acetylcysteine in mice: tissue-specific effects on glutathione concentrations. Carcinogenesis 16:2099–106
   PubMed Web of Science ®Google Scholar
• Minematsu T, Hashimoto T, Aoki T, et al. (2008). Role of organic anion transporters in the pharmacokinetics of zonampanel, an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor antagonist, in rats. Drug Metab Dispos 36:1496–504
   PubMed Web of Science ®Google Scholar
• Neuwelt EA, Pagel MA, Hasler BP, et al. (2001). Therapeutic efficacy of aortic administration of n-acetylcysteine as a chemoprotectant against bone marrow toxicity after intracarotid administration of alkylators, with or without glutathione depletion in a rat model. Cancer Res 61:7868–74
   PubMed Web of Science ®Google Scholar
• Offen D, Gilgun-Sherki Y, Barhum Y, et al. (2004). A low molecular weight copper chelator crosses the blood-brain barrier and attenuates experimental autoimmune encephalomyelitis. J Neurochem 89:1241–51
   PubMed Web of Science ®Google Scholar
• Olsson B, Johansson M, Gabrielsson J, Bolme P. (1988). Pharmacokinetics and bioavailability of reduced and oxidized n-acetylcysteine. Eur J Clin Pharmacol 34:77–82
   PubMed Web of Science ®Google Scholar
• Pombrio JM, Giangreco A, Li L, et al. (2001). Mercapturic acids (n-acetylcysteine s-conjugates) as endogenous substrates for the renal organic anion transporter-1. Mol Pharmacol 60:1091–9
   PubMed Web of Science ®Google Scholar
• Prescott LF, Illingworth RN, Critchley JA, et al. (1979). Intravenous n-acetylcystine: the treatment of choice for paracetamol poisoning. Br Med J 2:1097–100
   PubMed Web of Science ®Google Scholar
• Rushworth GF, Megson IL. (2014). Existing and potential therapeutic uses for n-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol Ther 141:150–9
   PubMed Web of Science ®Google Scholar
• Samuni Y, Goldstein S, Dean OM, Berk M. (2013). The chemistry and biological activities of n-acetylcysteine. Biochim Biophys Acta 1830:4117–29
   PubMed Web of Science ®Google Scholar
• Sawchuk RJ, Hedaya MA. (1990). Modeling the enhanced uptake of zidovudine (azt) into cerebrospinal fluid. 1. Effect of probenecid. Pharm Res 7:332–8
   PubMed Web of Science ®Google Scholar
• Shimizu M, Fuse K, Okudaira K, et al. (2005). Contribution of OATP (organic anion-transporting polypeptide) family transporters to the hepatic uptake of fexofenadine in humans. Drug Metabo Dispos 33:1477–81
   PubMed Web of Science ®Google Scholar
• Tachikawa M, Ozeki G, Higuchi T, et al. (2012). Role of the blood-cerebrospinal fluid barrier transporter as a cerebral clearance system for prostaglandin e(2) produced in the brain. J Neurochem 123:750–60
   PubMed Web of Science ®Google Scholar
• Tahara H, Kusuhara H, Maeda K, et al. (2006). Inhibition of oat3-mediated renal uptake as a mechanism for drug-drug interaction between fexofenadine and probenecid. Drug Metab Dispos 34:743–7
   PubMed Web of Science ®Google Scholar
• Versantvoort CHM, Bagrij T, Wright KA, Twentyman PR. (1995). On the relationship between the probenecid-sensitive transport of daunorubicin or calcein and the glutathione status of cells overexpressing the multidrug resistance-associated protein (MRP). Int J Cancer 63:855–62
   PubMed Web of Science ®Google Scholar
• Wong SL, Van Belle K, Sawchuk RJ. (1993). Distributional transport kinetics of zidovudine between plasma and brain extracellular fluid/cerebrospinal fluid in the rabbit: investigation of the inhibitory effect of probenecid utilizing microdialysis. J Pharmacol Exp Ther 264:899–909
   PubMed Web of Science ®Google Scholar
• Zhou J, Coles LD, Kartha RV, et al. (2015). Intravenous administration of stable-labeled n-acetylcysteine demonstrates an indirect mechanism for boosting glutathione and improving redox status. J Pharm Sci 104:2619–26
   PubMed Web of Science ®Google Scholar