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. 2010 Jul;5(2):99-106.

Evidence of active transport involvement in morphine transport via MDCKII and MDCK-PGP cell lines

S O Mashayekhi  1 , M R Sattari, P A Routledge
Affiliations

Evidence of active transport involvement in morphine transport via MDCKII and MDCK-PGP cell lines

S O Mashayekhi et al. Res Pharm Sci. 2010 Jul.

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.

Keywords: Morphine transport; Multidrug resistance related protein; P-glycoprotein; Probenecid-sensitive transport.

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Figures

Fig. 1
Fig. 1
Effects of the presence of cyclosporin on morphine permeability via two cell lines (*P<0.01, **<0.001).
Fig. 2
Fig. 2
Effects of the presence of various transporters substances on morphine permeability via MDCKII cell lines (*P<0.05, **P<0.001).
Fig. 3
Fig. 3
Effect of M6G on morphine permeability via MDCKII cell lines.
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References

    1. Brodie B, Kurz H, Schanker L. The importance of dissociation constant and lipid solubility in influencing the passage of drugs into the cerebro-spinal fluid. J Pharmacol Exp Ther. 1960;130:20–25. - PubMed
    1. Schanker LS. Passage of drugs into and out of the central nervous system. Antimicrob Agents Chemother. Antimicrob Agents Chemother. 1965;5:1044–1050. - PubMed
    1. Oldendorf WH, Hyman S, Braun L, Oldendorf SZ. Blood-brain barrier: penetration of morphine, codeine, heroin, and methadone after carotid injection. Science. 1972;178:984–986. - PubMed
    1. Lotsch J, Schmidt R, Vetter G, Schmidt H, Niederberger E, Geisslinger G, et al. Increased CNS uptake and enhanced antinociception of morphine-6-glucuronide in rats after inhibition of P-glycoprotein. J Neurochem. 2002a;83:241–248. - PubMed
    1. Campbell WI. Rectal controlled-release morphine: plasma levels of morphine and its metabolites following the rectal administration of MST Continus 100 mg. J Clin Pharm Ther. 1996;21:65–71. - PubMed

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