β-Lactam Antibiotics as Substrates for OCTN2, an Organic Cation/Carnitine Transporter
Open accessAbstract
Therapeutic use of cephaloridine, a beta-lactam antibiotic, in humans is associated with carnitine deficiency. A potential mechanism for the development of carnitine deficiency is competition between cephaloridine and carnitine for the renal reabsorptive process. OCTN2 is an organic cation/carnitine transporter that is responsible for Na(+)-coupled transport of carnitine in the kidney and other tissues. We investigated the interaction of several beta-lactam antibiotics with OCTN2 using human cell lines that express the transporter constitutively as well as using cloned human and rat OCTN2s expressed heterologously in human cell lines. The beta-lactam antibiotics cephaloridine, cefoselis, cefepime, and cefluprenam were found to inhibit OCTN2-mediated carnitine transport. These antibiotics possess a quaternary nitrogen as does carnitine. Several other beta-lactam antibiotics that do not possess this structural feature did not interact with OCTN2. The interaction of cephaloridine with OCTN2 is competitive with respect to carnitine. Interestingly, many of the beta-lactam antibiotics that were not recognized by OCTN2 were good substrates for the H(+)-coupled peptide transporters PEPT1 and PEPT2. In contrast, cephaloridine, cefoselis, cefepime, and cefluprenam, which were recognized by OCTN2, did not interact with PEPT1 and PEPT2. The interaction of cephaloridine with OCTN2 was Na(+)-dependent, whereas the interaction of cefoselis and cefepime with OCTN2 was largely Na(+)-independent. Furthermore, the Na(+)-dependent, OCTN2-mediated cellular uptake of cephaloridine could be demonstrated by direct uptake measurements. These studies show that OCTN2 plays a crucial role in the pharmacokinetics and therapeutic efficacy of certain beta-lactam antibiotics such as cephaloridine and that cephaloridine-induced carnitine deficiency is likely to be due to inhibition of carnitine reabsorption in the kidney.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Organic cation/carnitine transporter-2 (OCTN2) transports carnitine, an essential cofactor for fatty acid oxidation in mitochondria.
“Organic cation/carnitine transporter-2 (OCTN2) transports carnitine, an essential cofactor for fatty acid oxidation in mitochondria (192).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [192]
Cites
Yung-Chi, C., & Prusoff, W. H. (1973) · Biochemical Pharmacology · doi:10.1016/0006-2952(73)90196-2 · Cited by 12,922 · see citing works
Tamai, I., Ohashi, R., Nezu, J., Yabuuchi, H., Oku, A., Shimane, M., Sai, Y., & Tsuji, A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.32.20378 · Cited by 696 · see citing works
Nezu, J., Tamai, I., Oku, A., Ohashi, R., Yabuuchi, H., Hashimoto, N., Nikaido, H., Sai, Y., Koizumi, A., Shoji, Y., et al. (1999) · Nature Genetics · doi:10.1038/5030 · Cited by 553 · see citing works
Human Intestinal H+/Peptide Cotransporter
Liang, R., Fei, Y.-J., Prasad, P. D., Ramamoorthy, S., Han, H. R., Yang‐Feng, T. L., Hediger, M. A., Ganapathy, V., & Leibach, F. H. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.12.6456 · Cited by 503 · see citing works
Self-citationWu, X., Prasad, P. D., Leibach, F. H., & Ganapathy, V. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8669 · Cited by 340 · see citing works
Self-citationWu, X., Huang, W. Y., Prasad, P. D., Seth, P., Rajan, D. P., Leibach, F. H., Chen, J., Conway, S. J., & Ganapathy, V. (1999) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)35056-6 · Cited by 330 · see citing works
Self-citationGanapathy, M. E., Brandsch, M., Prasad, P. D., Ganapathy, V., & Leibach, F. H. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.43.25672 · Cited by 274 · see citing works
Self-citationMolecular cloning of PEPT 2, a new member of the H+/peptide cotransporter family, from human kidney
Liu, W., Liang, R., Ramamoorthy, S., Fei, Y.-J., Ganapathy, M. E., Hediger, M. A., Ganapathy, V., & Leibach, F. H. (1995) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(95)80036-f · Cited by 260 · see citing works
Self-citationBretschneider, B., Brandsch, M., & Neubert, R. (1999) · Pharmaceutical Research · doi:10.1023/a:1018814627484 · Cited by 202 · see citing works
Mutations in the organic cation/carnitine transporter OCTN2 in primary carnitine deficiency
Wang, Y., Ye, J., Ganapathy, V., & Longo, N. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.5.2356 · Cited by 194 · see citing works
Self-citationMolecular Pharmacology of Organic Cation Transporters in Kidney
Koepsell, H., Gorboulev, V., & Arndt, P. (1999) · The Journal of Membrane Biology · doi:10.1007/s002329900475 · Cited by 155 · see citing works
Tang, N. L. S., Ganapathy, V., Wu, X., Hui, J., Seth, P., Yuen, P. M. P., Fok, T. F., & Hjelm, N. M. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.4.655 · Cited by 153 · see citing works
Self-citationBindingDB (2013) · PubMed · doi:10.7270/q2h41sjq · Cited by 126 · see citing works
Rebouche, C. J., & Mack, D. L. (1984) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(84)90212-1 · Cited by 110 · see citing works
GENETIC DISORDERS OF CARNITINE METABOLISM AND THEIR NUTRITIONAL MANAGEMENT
Kerner, J., & Hoppel, C. L. (1998) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.18.1.179 · Cited by 108 · see citing works
Wenzel, U., Gebert, I., Weintraut, H., Weber, W. M., Clauss, W. G., & Daniel, H. (1996) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)12941-8 · Cited by 97 · see citing works
Mechanisms of cephalosporin nephrotoxicity: A comparison of cephaloridine and cephaloglycin
Tune, B. M., & Fravert, D. G. (1980) · Kidney International · doi:10.1038/ki.1980.177 · Cited by 94 · see citing works
Ganapathy, M. E., Prasad, P. D., Mackenzie, B., Ganapathy, V., & Leibach, F. H. (1997) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/s0005-2736(96)00234-9 · Cited by 93 · see citing works
Self-citationCharacterization of l -carnitine transport by rat kidney brush-border-membrane vesicles
Stieger, B., O’Neill, B., & Krähenbühl, S. (1995) · Biochemical Journal · doi:10.1042/bj3090643 · Cited by 76 · see citing works
Ramamoorthy, S., Liu, W., Ma, Y.-Y., Yang‐Feng, T. L., Ganapathy, V., & Leibach, F. H. (1995) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(95)00178-7 · Cited by 75 · see citing works
Self-citationBurwinkel, B., Kreuder, J. G., Schweitzer, S., Vorgerd, M., Gempel, K. E., Gerbitz, K.-D., & Kilimann, M. W. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.1060 · Cited by 68 · see citing works
Carnitine Uptake Defect: Frameshift Mutations in the Human Plasmalemmal Carnitine Transporter Gene
Lamhonwah, A., & Tein, I. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9679 · Cited by 64 · see citing works
Daniel, H., & Adibi, S. A. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116824 · Cited by 59 · see citing works
Tsuji, A., Tamai, I., Nakanishi, M., Terasaki, T., & Hamano, S. (1993) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.1993.tb05645.x · Cited by 50 · see citing works
Separation of isomeric glycoflavones by high-pressure liquid chromatography
Becker, H., Wilking, G., & Hostettmann, K. (1977) · Journal of Chromatography A · doi:10.1016/s0021-9673(00)83009-5 · Cited by 36 · see citing works
Tune, B. M., & Hsu, C. Y. (1994) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)22555-1 · Cited by 35 · see citing works
Sodium-dependent carnitine transport in human placental choriocarcinoma cells
Prasad, P. D., Huang, W. Y., Ramamoorthy, S., Carter, A. L., Leibach, F. H., & Ganapathy, V. (1996) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(96)00126-5 · Cited by 34 · see citing works
Self-citationSodium-dependent high-affinity binding of carnitine to human placental brush border membranes
Roque, A. S., Prasad, P. D., Bhatia, J., Leibach, F. H., & Ganapathy, V. (1996) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(96)00068-5 · Cited by 25 · see citing works
Self-citationHuang, W., Shaikh, S. N., Ganapathy, M. E., Hopfer, U., Leibach, F. H., Carter, A. L., & Ganapathy, V. (1999) · Biochemical Pharmacology · doi:10.1016/s0006-2952(99)00219-1 · Cited by 22 · see citing works
Self-citationDetermination of cephaloridine in serum and tissue by high-performance liquid chromatography
Wold, J. S., & Turnipseed, S. A. (1977) · Journal of Chromatography A · doi:10.1016/s0021-9673(00)83008-3 · Cited by 18 · see citing works
Effects of l-carnitine on the renal tubular transport of cephaloridine
Tune, B. M. (1995) · Biochemical Pharmacology · doi:10.1016/0006-2952(95)00169-z · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Blood-Brain Barrier: From Physiology to Disease and Back
Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,294 · see citing works
Koepsell, H., Lips, K. S., & Volk, C. (2007) · Pharmaceutical Research · doi:10.1007/s11095-007-9254-z · Cited by 984 · see citing works
Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation
Klaassen, C. D., & Aleksunes, L. M. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002014 · Cited by 808 · see citing works
Carrier-mediated cellular uptake of pharmaceutical drugs: an exception or the rule?
Dobson, P. D., & Kell, D. B. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2438 · Cited by 475 · see citing works
Molecular and Cellular Physiology of Renal Organic Cation and Anion Transport
Wright, S. H., & Dantzler, W. H. (2004) · Physiological Reviews · doi:10.1152/physrev.00040.2003 · Cited by 404 · see citing works
EVALUATION OF DRUG-DRUG INTERACTION IN THE HEPATOBILIARY AND RENAL TRANSPORT OF DRUGS
Shitara, Y., Sato, H., & Sugiyama, Y. (2005) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.44.101802.121444 · Cited by 336 · see citing works
Renal Transporters in Drug Development
Morrissey, K. M., STOCKER, S. L., Wittwer, M., Xu, L., & Giacomini, K. M. (2012) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011112-140317 · Cited by 326 · see citing works
Koepsell, H., Schmitt, B. M., & Gorboulev, V. (2003) · Springer eBooks · doi:10.1007/s10254-003-0017-x · Cited by 318 · see citing works
Pharmacokinetics of L-Carnitine
Evans, A. M., & Fornasini, G. (2003) · Clinical Pharmacokinetics · doi:10.2165/00003088-200342110-00002 · Cited by 303 · see citing works
Dresser, M., Leabman, M. K., & Giacomini, K. (2001) · Journal of Pharmacy and Science · doi:10.1002/1520-6017(200104)90:4 · Cited by 285 · see citing works
Mammalian peptide transporters as targets for drug delivery
Rubio‐Aliaga, I., & Daniel, H. (2002) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(02)02072-2 · Cited by 240 · see citing works
Pharmaceutical and pharmacological importance of peptide transporters
Brandsch, M., Knütter, I., & Bosse-Doenecke, E. (2008) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp.60.5.0002 · Cited by 224 · see citing works
Transporters and Renal Drug Elimination
Lee, W., & Kim, R. B. (2004) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.44.101802.121856 · Cited by 222 · see citing works
Renal Drug Transporters and Drug Interactions
Ivanyuk, A., Livio, F., Biollaz, J., & Buclin, T. (2017) · Clinical Pharmacokinetics · doi:10.1007/s40262-017-0506-8 · Cited by 221 · see citing works
Drug uptake systems in liver and kidney.
van Montfoort, J. V., Hagenbuch, B., Groothuis, G. M., Koepsell, H., Meier, P. J., & Meijer, D. (2003) · Current drug metabolism · doi:10.2174/1389200033489460 · Cited by 9 · see citing works
Nakanishi, T., Hatanaka, T., Huang, W. Y., Prasad, P. D., Leibach, F. H., Ganapathy, M. E., & Ganapathy, V. (2001) · The Journal of Physiology · doi:10.1111/j.1469-7793.2001.0297f.x · Cited by 194 · see citing works
Self-citationMDR1 Genotype-Related Pharmacokinetics and Pharmacodynamics.
Sakaeda, T., Nakamura, T., & Okumura, K. (2002) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.25.1391 · Cited by 190 · see citing works
Tissue Distribution and Renal Developmental Changes in Rat Organic Cation Transporter mRNA levels
Slitt, A. L., Cherrington, N. J., Hartley, D. P., Leazer, T. M., & Klaassen, C. D. (2002) · Drug Metabolism and Disposition · doi:10.1124/dmd.30.2.212 · Cited by 169 · see citing works
Xenobiotic transporters and kidney injury
George, B., You, D., Joy, M. S., & Aleksunes, L. M. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.01.005 · Cited by 142 · see citing works
Carnitine transport: Pathophysiology and metabolism of known molecular defects
Tein, I. (2003) · Journal of Inherited Metabolic Disease · doi:10.1023/a:1024481016187 · Cited by 140 · see citing works
Tamai, I. (2013) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.1816 · Cited by 141 · see citing works
Cellular pharmacodynamics and pharmacokinetics of antibiotics: current views and perspectives.
Françoise Van Bambeke, A., Barcia-Macay, M., Lemaire, S., & Tulkens, P. M. (2006) · PubMed · Cited by 138 · see citing works
Placental transporters relevant to drug distribution across the maternal-fetal interface.
Ganapathy, V., Prasad, P., Ganapathy, M. E., & Leibach, F. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)39087-1 · Cited by 144 · see citing works
Self-citationCarnitine Transport by Organic Cation Transporters and Systemic Carnitine Deficiency
Lahjouji, K., Mitchell, G. A., & Qureshi, I. A. (2001) · Molecular Genetics and Metabolism · doi:10.1006/mgme.2001.3207 · Cited by 133 · see citing works
Transcriptional profiling of genes induced in the livers of patients treated with carbamazepine
Oscarson, M., Zanger, U. M., Rifki, O. F., KLEIN, K., Eichelbaum, M. F., & Meyer, U. (2006) · Clinical Pharmacology & Therapeutics · doi:10.1016/j.clpt.2006.08.013 · Cited by 132 · see citing works
Intestinal drug efflux: formulation and food effects
Wagner, D., Spahn-Langguth, H., Hanafy, A., Koggel, A., & Langguth, P. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(01)00183-1 · Cited by 127 · see citing works
Assessment of the Role of Renal Organic Anion Transporters in Drug-Induced Nephrotoxicity
Hagos, Y., & Wolff, N. A. (2010) · Toxins · doi:10.3390/toxins2082055 · Cited by 126 · see citing works
Revisiting the blood-brain barrier: A hard nut to crack in the transportation of drug molecules
Harilal, S., Jose, J., Parambi, D. G. T., Kumar, R., Unnikrishnan, M. K., Uddin, M. S., Mathew, G. E., Pratap, R., Marathakam, A., & Mathew, B. (2020) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2020.03.018 · Cited by 124 · see citing works
Uptake of Cardiovascular Drugs Into the Human Heart
Grube, M., zu Schwabedissen, H. E. M., Präger, D., Haney, J., Möritz, K.-U., Meissner, K., Rosskopf, D., Eckel, L., Böhm, M., Jedlitschky, G., et al. (2006) · Circulation · doi:10.1161/circulationaha.105.586107 · Cited by 118 · see citing works
Carnitine: transport and physiological functions in the brain
NACZ, K. (2004) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2004.06.001 · Cited by 115 · see citing works
Grube, M., zu Schwabedissen, H. E. M., Draber, K., Präger, D., Möritz, K.-U., Linnemann, K., Fusch, C., Jedlitschky, G., & Kroemer, H. K. (2004) · Drug Metabolism and Disposition · doi:10.1124/dmd.104.001560 · Cited by 111 · see citing works
Regulation of organic cation transport
Ciarimboli, G., & Schlatter, E. (2005) · Pflügers Archiv · doi:10.1007/s00424-004-1355-5 · Cited by 114 · see citing works
OCTN Cation Transporters in Health and Disease
Pochini, L., Scalise, M., Galluccio, M., & Indiveri, C. (2013) · Journal of biomolecular screening · doi:10.1177/1087057113493006 · Cited by 99 · see citing works
Françoise Van Bambeke, A. (2003) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkg225 · Cited by 101 · see citing works
The Developing Kidney and Environmental Toxins
Solhaug, M. J., Bolger, P. M., & José, P. A. (2004) · PEDIATRICS · doi:10.1542/peds.113.s3.1084 · Cited by 96 · see citing works
Transporter-mediated Drug Interactions
Tsuji, A. (2002) · Drug Metabolism and Pharmacokinetics · doi:10.2133/dmpk.17.253 · Cited by 94 · see citing works
Organic Cation Transporters in Human Physiology, Pharmacology, and Toxicology
Samodelov, S. L., Kullak-Ublick, G. A., Gai, Z., & Visentin, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21217890 · Cited by 91 · see citing works
Pharmacokinetics and pharmacodynamics of cefovecin in dogs
Stegemann, M. R., Sherington, J., & BLANCHFLOWER, S. E. (2006) · Journal of Veterinary Pharmacology and Therapeutics · doi:10.1111/j.1365-2885.2006.00801.x · Cited by 85 · see citing works
Ullán, R. V., Liu, G., Casqueiro, J., Gutiérrez, S., Bañuelos, Ó., & Martin, J. F. (2002) · Molecular Genetics and Genomics · doi:10.1007/s00438-002-0702-5 · Cited by 84 · see citing works
Drugdrug interactions involving membrane transporters in the human kidney
Li, M., Anderson, G. D., & Wang, J. (2006) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2.4.505 · Cited by 84 · see citing works
Grigat, S., Fork, C., Bach, M., Gölz, S., Geerts, A., Schömig, E., & Gründemann, D. (2008) · Drug Metabolism and Disposition · doi:10.1124/dmd.108.023929 · Cited by 81 · see citing works
Role of organic cation transporters in drug-induced toxicity
Ciarimboli, G. (2011) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2011.547474 · Cited by 87 · see citing works
Lahjouji, K., Elimrani, I., Lafond, J., Leduc, L., Qureshi, I. A., & Mitchell, G. A. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00333.2003 · Cited by 77 · see citing works
Kato, Y., Takahara, S., Kato, S., Kubo, Y., Sai, Y., Tamai, I., Yabuuchi, H., & Tsuji, A. (2008) · Drug Metabolism and Disposition · doi:10.1124/dmd.107.019125 · Cited by 72 · see citing works
Solute Carriers in the Blood–Brain Barier: Safety in Abundance
Nałęcz, K. A. (2016) · Neurochemical Research · doi:10.1007/s11064-016-2030-x · Cited by 69 · see citing works
Juraszek, B., & Nałęcz, K. A. (2019) · Molecules · doi:10.3390/molecules25010014 · Cited by 68 · see citing works
Ohashi, R., Tamai, I., Inano, A., Katsura, M., Sai, Y., Nezu, J., & Tsuji, A. (2002) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.036004 · Cited by 67 · see citing works
Hosoya, K., Tomi, M., & Tachikawa, M. (2011) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2011.628983 · Cited by 65 · see citing works
Inhibition of OCTN2-Mediated Transport of Carnitine by Etoposide
Hu, C., Lancaster, C. S., Zuo, Z., Hu, S., Chen, Z., Rubnitz, J. E., Baker, S. D., & Sparreboom, A. (2012) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0980 · Cited by 65 · see citing works
Role of transporters in placental transfer of drugs.
Ganapathy, V., & Prasad, P. (2005) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2005.02.023 · Cited by 71 · see citing works
Self-citationHirano, T., Yasuda, S., Osaka, Y., Kobayashi, M., Itagaki, S., & Iseki, K. (2006) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2006.07.002 · Cited by 59 · see citing works
Self-citationRecent advances in drug delivery via the organic cation/carnitine transporter 2 (OCTN2/SLC22A5)
Kou, L., Sun, R., Ganapathy, V., Yao, Q., & Chen, R. (2018) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2018.1502273 · Cited by 58 · see citing works
Self-citationExcretion of biliary compounds during intrauterine life
Macı́as, R. I. R., Marı́n, J. J. G., & Serrano, M. A. (2009) · World Journal of Gastroenterology · doi:10.3748/wjg.15.817 · Cited by 58 · see citing works
Cisplatin-Induced Downregulation of OCTN2 Affects Carnitine Wasting
Lancaster, C. S., Hu, C., Franke, R. M., Filipski, K. K., Orwick, S. J., Chen, Z., Zuo, Z., Loos, W. J., & Sparreboom, A. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-1239 · Cited by 55 · see citing works
Pharmacokinetics of cefovecin in cats
Stegemann, M. R., Sherington, J., Coati, N., BROWN, S. A., & BLANCHFLOWER, S. E. (2006) · Journal of Veterinary Pharmacology and Therapeutics · doi:10.1111/j.1365-2885.2006.00795.x · Cited by 55 · see citing works
Sayed‐Ahmed, M. M., Al‐Shabanah, O. A., Hafez, M. M., Aleisa, A. M., & Al-Rejaie, S. S. (2010) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.05.002 · Cited by 53 · see citing works
Interaction of β-lactam antibiotics with the mitochondrial carnitine/acylcarnitine transporter
Pochini, L., Galluccio, M., Scumaci, D., Giangregorio, N., Tonazzi, A., Palmieri, F., & Indiveri, C. (2008) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2008.03.003 · Cited by 52 · see citing works
Long-chain Acyl-CoA Dehydrogenase Deficiency as a Cause of Pulmonary Surfactant Dysfunction
Goetzman, E. S., Alcorn, J. F., Bharathi, S. S., Uppala, R., McHugh, K. J., Kośmider, B., Chen, R., Zuo, Y. Y., Beck, M. E., McKinney, R. W., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.540260 · Cited by 51 · see citing works
Treating Alzheimer’s disease using nanoparticle-mediated drug delivery strategies/systems
Roghani, A. K., Garcia, R. I., Roghani, A., Reddy, A. P., Khemka, S., Reddy, R. P., Pattoor, V., Jacob, M., Reddy, P. H., & Sehar, U. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102291 · Cited by 53 · see citing works
Potential Antibiotics for the Treatment of Neonatal Sepsis Caused by Multidrug-Resistant Bacteria
Darlow, C. A., da Costa, R. M. A., Ellis, S., Franceschi, F. J., Sharland, M., Piddock, L. J. V., Das, S., & Hope, W. W. (2021) · Pediatric Drugs · doi:10.1007/s40272-021-00465-z · Cited by 47 · see citing works
Haschke, M., Vitins, T., Lude, S., Todesco, L., Novakova, K., Herrmann, R., & Krähenbühl, S. (2009) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfp456 · Cited by 46 · see citing works
Fisel, P., Renner, O., Nies, A. T., Schwab, M. G., & Schaeffeler, E. (2014) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2014.876990 · Cited by 43 · see citing works
Giacomini, M. M., Jia, H., Liang, X., Chandrasekhar, J., Twelves, J., Whitney, J. A., Lepist, E., & Ray, A. S. (2016) · Drug Metabolism and Disposition · doi:10.1124/dmd.116.073338 · Cited by 42 · see citing works
Waldner, R., Laschan, C., Lohninger, A., Gessner, M., Tüchler, H., Huemer, M., Spiegel, W., & Karlic, H. (2005) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-005-0054-8 · Cited by 41 · see citing works
Tonazzi, A., Giangregorio, N., Console, L., & Indiveri, C. (2015) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/138955751505150408142032 · Cited by 40 · see citing works
Iwata, D., Kato, Y., Wakayama, T., Sai, Y., Kubo, Y., Iseki, S., & Tsuji, A. (2008) · Drug Metabolism and Pharmacokinetics · doi:10.2133/dmpk.23.207 · Cited by 40 · see citing works
Zacharias, H. U., Schley, G., Hochrein, J., Klein, M. S., Köberle, C., Eckardt, K., Willam, C., Oefner, P. J., & Gronwald, W. (2012) · Metabolomics · doi:10.1007/s11306-012-0479-4 · Cited by 39 · see citing works
Diao, L., Ekins, S., & Polli, J. E. (2009) · Pharmaceutical Research · doi:10.1007/s11095-009-9905-3 · Cited by 38 · see citing works
Colistin is Substrate of the Carnitine/Organic Cation Transporter 2 (OCTN2, SLC22A5)
Visentin, M., Gai, Z., Torozi, A., Hiller, C., & Kullak-Ublick, G. A. (2017) · Drug Metabolism and Disposition · doi:10.1124/dmd.117.077248 · Cited by 38 · see citing works
Tahara, H., Yee, S. W., Urban, T. J., Hesselson, S., Castro, R. A., Kawamoto, M., Stryke, D., Johns, S. J., Ferrin, T. E., Kwok, P., et al. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.108.146449 · Cited by 38 · see citing works
Carnitine/xenobiotics transporters in the human mammary gland epithelia, MCF12A.
Kwok, B., Yamauchi, A., Rajesan, R., Chan, L., Dhillon, U., Gao, W., Xu, H., Wang, B., Takahashi, S., Semple, J., et al. (2006) · American Journal of Physiology. Regulatory Integrative and Comparative Physiology · doi:10.1152/ajpregu.00087.2005 · Cited by 41 · see citing works
Hucke, A., & Ciarimboli, G. (2016) · Journal of clinical pharmacology · doi:10.1002/jcph.706 · Cited by 36 · see citing works
Atkinson, D. E., BOYD, R., & Sibley, C. P. (2006) · Elsevier eBooks · doi:10.1016/b978-012515400-0/50057-9 · Cited by 36 · see citing works
Tsuji, A. (2006) · Journal of Infection and Chemotherapy · doi:10.1007/s10156-006-0478-3 · Cited by 35 · see citing works
Diao, L., Ekins, S., & Polli, J. E. (2010) · Molecular Pharmaceutics · doi:10.1021/mp100226q · Cited by 32 · see citing works
Kumar, R., Singh, H., Mazumder, A., Salahuddin, S., & Yadav, R. K. (2023) · Topics in Current Chemistry · doi:10.1007/s41061-023-00422-z · Cited by 32 · see citing works
OCTN2-Mediated Carnitine Uptake in a Newly Discovered Human Proximal Tubule Cell Line (Caki-1)
Glube, N. D., Closs, E. I., & Langguth, P. (2006) · Molecular Pharmaceutics · doi:10.1021/mp060073a · Cited by 32 · see citing works
Use of the Øie-Tozer Model in Understanding Mechanisms and Determinants of Drug Distribution
Waters, N. J., & Lombardo, F. (2010) · Drug Metabolism and Disposition · doi:10.1124/dmd.110.032458 · Cited by 32 · see citing works
Proctor, W. R., Ming, X., Bourdet, D. L., Han, T. K., Everett, R., & Thakker, D. R. (2016) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2015.11.040 · Cited by 31 · see citing works
Rytting, E., & Audus, K. L. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.072363 · Cited by 31 · see citing works
Loots, D. T., Mienie, L. J., Bergh, J. J., & der Schyf, C. J. V. (2004) · Life Sciences · doi:10.1016/j.lfs.2004.03.007 · Cited by 29 · see citing works
High Affinity Carnitine Transporters from OCTN Family in Neural Cells
Januszewicz, E., Bekisz, M., Mozrzymas, J. W., & Nałęcz, K. A. (2010) · Neurochemical Research · doi:10.1007/s11064-010-0131-5 · Cited by 30 · see citing works
Overview of the Components of Cardiac Metabolism
Hausner, E. A., Elmore, S. A., & Yang, X. (2019) · Drug Metabolism and Disposition · doi:10.1124/dmd.119.086611 · Cited by 28 · see citing works
Kano, T., Kato, Y., Ito, K., Ogihara, T., Kubo, Y., & Tsuji, A. (2009) · Drug Metabolism and Disposition · doi:10.1124/dmd.108.025015 · Cited by 28 · see citing works
Lepist, E., & Ray, A. S. (2017) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2017.1372425 · Cited by 27 · see citing works
Khosravi, A. R., Jayaram, B., Goliaei, B., & Masoudi‐Nejad, A. (2019) · Molecular Medicine · doi:10.1186/s10020-019-0098-x · Cited by 26 · see citing works
Mancinelli, A., D'Iddio, S., Bisonni, R., Graziano, F., Lippe, P., & Calvani, M. (2006) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-006-0341-3 · Cited by 26 · see citing works
Cheng, Y., El‐Kattan, A. F., Zhang, Y., Ray, A. S., & Lai, Y. (2016) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.5b00511 · Cited by 26 · see citing works
Lee, N.-Y., Choi, H.-O., & Kang, Y. (2012) · Neurochemical Research · doi:10.1007/s11064-012-0723-3 · Cited by 24 · see citing works
Upregulation of mammary gland OCTNs maintains carnitine homeostasis in suckling infants
Lamhonwah, A., Mai, L., Chung, C., Lamhonwah, D., Ackerley, C. A., & Tein, I. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.12.100 · Cited by 24 · see citing works
Tonazzi, A., Eberini, I., & Indiveri, C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0082286 · Cited by 24 · see citing works
Ling, B., & Alcorn, J. (2008) · Journal of Nutrition · doi:10.1093/jn/138.7.1317 · Cited by 24 · see citing works
Diao, L., & Polli, J. E. (2011) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22557 · Cited by 23 · see citing works
Jafari, A., Dashti‐Khavidaki, S., Khalili, H., & Lessan‐Pezeshki, M. (2013) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2013.794217 · Cited by 22 · see citing works
Girardin, M., Dionne, S., Goyette, P., Rioux, J. D., Bitton, A., Elimrani, I., Charlebois, P., Qureshi, I. A., Levy, E. H., & Seidman, E. G. (2011) · Journal of Crohn s and Colitis · doi:10.1016/j.crohns.2011.08.003 · Cited by 21 · see citing works
Czeredys, M., Samluk, Ł., Michalec, K., Tułodziecka, K., Skowronek, K. J., & Nałęcz, K. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0082105 · Cited by 21 · see citing works
Drug Transporters and Na+/H+ Exchange Regulatory Factor PSD-95/Drosophila Discs Large/ZO-1 Proteins
Walsh, D. R., Nolin, T. D., & Friedman, P. A. (2015) · Pharmacological Reviews · doi:10.1124/pr.115.010728 · Cited by 21 · see citing works
Arabidopsis thalianaMitochondrial Glyoxalase 2-1 Exhibits β-Lactamase Activity
Limphong, P., Nimako, G. K., Thomas, P. W., Fast, W. L., Makaroff, C. A., & Crowder, M. W. (2009) · Biochemistry · doi:10.1021/bi9010539 · Cited by 21 · see citing works
Liu, Z., & Liu, K. (2013) · Asian Journal of Pharmaceutical Sciences · doi:10.1016/j.ajps.2013.07.020 · Cited by 20 · see citing works
Todesco, L., Bur, D., Brooks, H., Török, M., Landmann, L., Stieger, B., & Krähenbühl, S. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8065-7 · Cited by 20 · see citing works
- Authors
- Ganapathy, M. E., Huang, W., Rajan, D. P., Carter, A. L., Sugawara, M., Iseki, K., Leibach, F. H., & Ganapathy, V.
- Affiliations
- Augusta University (US)
- Hokkaido University Hospital (JP)
- Corresponding author
- Ganapathy, Malliga E.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-01
- Volume
- 275
- Issue
- 3
- Pages
- 1699-1707
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1966267502
- Cited by
- 175
- References
- 31
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 5 · 2022: 2 · 2021: 3 · 2020: 7 · 2019: 6 · 2018: 5 · 2017: 7 · 2016: 8 · 2015: 8 · 2014: 3 · 2013: 7 · 2012: 9
- FWCI
- 3.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01gm054412-03)
- National Institute of General Medical Sciences (GM54412)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- OCTN2, beta-lactam antibiotics, cephaloridine, carnitine deficiency, competitive inhibition, PepT1, PEPT2, cefepime, pharmacokinetics, drug-transporter interactions
- MeSH terms
- Solute Carrier Family 22 Member 5, Cefepime, Acetylcarnitine, Animals, Anti-Bacterial Agents, Carnitine, Carrier Proteins, Cefadroxil, Cephaloridine, Cephalosporins, Dose-Response Relationship, Drug, HeLa Cells, Humans, Kinetics, Membrane Proteins, Nitrogen, Sodium, Tumor Cells, Cultured, Organic Cation Transport Proteins, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review