title: Evidence of active transport involvement in morphine transport via MDCKII and MDCK-PGP cell lines.
abstract: Several transporters appear to be important in transporting various drugs. Many patients, who receive morphine as analgesic medication, also receive other medications with potency of changing morphine transport by affecting P-glycoprotein (P-GP) and oatp2 transport system. This could influence morphine pharmacokinetics and pharmacodynamics. The aim of present study was to elucidate the transport mechanisms involved in transporting morphine via MDCKII and MDCK-PGP cells. Morphine permeability was examined in the presence of various compounds with ability in inhibiting different transport systems including: digoxin, probenecid and d- glucose. The effect of morphine concentration changes on its transport was also examined. Morphine concentration was measured using HPLC with electrochemical detector. Morphine permeability via a MDCK II cells was greater than sucrose permeability, and reduced when a P-GP expressed cell line was used. Its permeability was increased significantly in the presence of a strong P-GP inhibitor. Morphine permeability decreased significantly in the presence of digoxin but not in the presence of d-glucose or probenecid. These results showed that morphine was a P-GP substrate, and digoxin related transporters such as oatp2 were involved in its transport. Morphine was not substrate for glucose or probenecid-sensitive transporters.
authors: National Public Health Management Research Center, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, I.R.Iran.
authors: S O
authors: SO
authors: Mashayekhi
authors: M R
authors: MR
authors: Sattari
authors: P A
authors: PA
authors: Routledge
references: J Neurochem. 2007 Sep;102(5):1677-1690
references: 17697052
references: J Neurochem. 2003 Sep;86(6):1564-7
references: 12950465
references: J Neurol. 2002 Jan;249(1):9-17
references: 11954874
references: Br J Pharmacol. 2000 Dec;131(8):1784-92
references: 11139459
references: Biochem Pharmacol. 1993 Sep 14;46(6):961-8
references: 8216355
references: Br J Pharmacol. 2007 Jul;151(5):701-12
references: 17471182
references: J Pain Palliat Care Pharmacother. 2007;21(4):5-12
references: 18032310
references: Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7114-8
references: 8041755
references: J Clin Pharm Ther. 1996 Apr;21(2):65-71
references: 8809641
references: Anticancer Drugs. 1996 Jul;7(5):568-78
references: 8862725
references: Antimicrob Agents Chemother (Bethesda). 1965;5:1044-50
references: 5883399
references: Anesthesiology. 2002 Apr;96(4):913-20
references: 11964599
references: J Histochem Cytochem. 1990 Sep;38(9):1277-87
references: 1974900
references: J Pharmacol Exp Ther. 1960 Sep;130:20-5
references: 13804623
references: Pharm Res. 2002 Jun;19(6):738-43
references: 12134942
references: Int J Clin Pharmacol Ther. 1998 Feb;36(2):69-70
references: 9520146
references: Drug Metab Dispos. 1997 Jun;25(6):768-71
references: 9193881
references: J Pharmacol Exp Ther. 2003 Jan;304(1):441-52
references: 12490621
references: J Clin Pharm Ther. 2008 Aug;33(4):419-27
references: 18613860
references: Exp Nephrol. 1998 Mar-Apr;6(2):89-97
references: 9567214
references: Biochem Pharmacol. 1999 Sep 15;58(6):951-7
references: 10509747
references: Science. 1972 Dec 1;178(4064):984-6
references: 5084666
references: J Biol Chem. 1993 Sep 15;268(26):19161-4
references: 8366068
references: Biopharm Drug Dispos. 2009 Apr;30(3):99-106
references: 19260034
references: Brain Res. 1995 Sep 25;693(1-2):187-95
references: 8653407
references: J Pain Symptom Manage. 2003 May;25(5 Suppl):S4-S11
references: 12694987
references: J Neurochem. 2002 Oct;83(2):241-8
references: 12423235
references: Clin Pharmacol Ther. 2008 Apr;83(4):559-66
references: 17898703