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Pathway Description
Methylphenidate Metabolism
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2022-03-22
Last Updated: 2023-10-25
Methylphenidate is taken orally as any of the brand names Adhansia, Aptensio, Biphentin, Concerta, Cotempla, Daytrana, Foquest, Jornay, Metadate, Methylin, Quillichew, Quillivant, Relexxii, or Ritalin. Methylphenidate is rapidly absorbed from the small intestine into the blood stream via the transporter P-glycoprotein or through diffusion. Methylphenidate can diffuse through many membranes, but P-glycoprotein has been found to help transport the drug some of the time. From there it travels to the liver where it is likely transported in by P-glycoprotein. In the liver Methylphenidate is metabolized by Carboxylesterase 1A1 into Ritalinic acid. While other Carboxylesterase are well understood, this one is less well understood and studied so it is unknown where exactly in the liver this metabolism takes place. 60%-86% is metabolized into ritalinic acid. This is transported out of the liver likely again by P-glycoprotein back into the blood vessel where it travels to the kidney and is excreted renally. A very small portion is excreted as Methylphenidate. 78%-97% is excreted as Ritalinc acid. Some is excreted as minor other metatbolites.
References
Methylphenidate Metabolism References
Zhu HJ, Wang JS, Donovan JL, Jiang Y, Gibson BB, DeVane CL, Markowitz JS: Interactions of attention-deficit/hyperactivity disorder therapeutic agents with the efflux transporter P-glycoprotein. Eur J Pharmacol. 2008 Jan 14;578(2-3):148-58. doi: 10.1016/j.ejphar.2007.09.035. Epub 2007 Oct 5.
Pubmed: 17963743
Sun Z, Murry DJ, Sanghani SP, Davis WI, Kedishvili NY, Zou Q, Hurley TD, Bosron WF: Methylphenidate is stereoselectively hydrolyzed by human carboxylesterase CES1A1. J Pharmacol Exp Ther. 2004 Aug;310(2):469-76. doi: 10.1124/jpet.104.067116. Epub 2004 Apr 13.
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Tamai I, Nezu J, Uchino H, Sai Y, Oku A, Shimane M, Tsuji A: Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun. 2000 Jun 24;273(1):251-60. doi: 10.1006/bbrc.2000.2922.
Pubmed: 10873595
Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 1998 Dec 31;5(6):355-64. doi: 10.1093/dnares/5.6.355.
Pubmed: 10048485
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
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