+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

Influence of probenecid on the delivery of morphine-6-glucuronide to the brain

Influence of probenecid on the delivery of morphine-6-glucuronide to the brain

European Journal of Pharmaceutical Sciences 24(1): 49-57

The objective was to evaluate the influence of probenecid on the blood-brain barrier (BBB) transport of morphine-6-glucuronide (M6G). Microdialysis probes were placed in the striatum and into the jugular vein of Sprague-Dawley rats. Each probe was calibrated in vivo using retrodialysis by drug. M6G was administered as a 4-h exponential i.v. infusion, and the experiment was repeated the following day with the addition of probenecid. The data were analysed using NONMEM. An integrated model including the total arterial concentrations, the dialysate concentrations in brain and blood, and the recovery measurements, was developed. The extent of BBB transport, expressed as the ratio between clearance into the brain and clearance out of the brain (CLin/CLout), was estimated as 0.29 on both days, indicating that efflux transporters act on M6G at the BBB. However, the probenecid-sensitive transporters are not involved in the brain efflux, as the ratio was unaltered although probenecid was co-administered. In contrast, the systemic elimination of M6G decreased by 22% (p < 0.05) upon probenecid co-administration. The half-life of M6G was longer in the brain than in blood on both experimental days (p < 0.05). In conclusion, probenecid decreased the systemic elimination of M6G, but had no effect on the BBB transport of M6G. Copyright 2004 Elsevier B.V. All rights reserved.

(PDF emailed within 0-6 h: $19.90)

Accession: 012210823

Download citation: RISBibTeXText

PMID: 15626577

DOI: 10.1016/j.ejps.2004.09.009

Related references

A validated method for simultaneous determination of codeine, codeine-6-glucuronide, norcodeine, morphine, morphine-3-glucuronide and morphine-6-glucuronide in post-mortem blood, vitreous fluid, muscle, fat and brain tissue by LC-MS. Journal of Analytical Toxicology 39(3): 203-212, 2016

Influence of renal failure on the disposition of morphine, morphine-3-glucuronide and morphine-6-glucuronide in sheep during intravenous infusion with morphine. Journal of Pharmacology and Experimental Therapeutics 282(2): 779-786, 1997

The influence of inhibition of probenecid sensitive transporters on the central nervous system (CNS) uptake and the antinociceptive activity of morphine-6-glucuronide in rats. Neuroscience Letters 329(2): 145-148, 2002

Influence of ranitidine on the morphine-3-glucuronide to morphine-6-glucuronide ration after oral administration of morphine in humans. Human & Experimental Toxicology 17(6): 347-352, June, 1998

Morphine-6-glucuronide is responsible for the analgesic effect after morphine administration: a quantitative review of morphine, morphine-6-glucuronide, and morphine-3-glucuronide. British Journal of Anaesthesia 113(6): 935-944, 2015

The influence of age on the distribution of morphine and morphine-3-glucuronide across the blood-brain barrier in sheep. British Journal of Pharmacology 157(6): 1085-1096, 2010

Biochemical basis for analgesic activity of morphine 6 glucuronide part 1 penetration of morphine 6 glucuronide in the brain of rats. Biochemical Pharmacology: 1423-1430, 1973

Biochemical basis for analgesic activity of morphine-6-glucuronide. I. Penetration of morphine-6-glucuronide in the brain of rats. Biochemical Pharmacology 22(12): 1423-1430, 1973

Poor permeability of morphine 3-glucuronide and morphine 6-glucuronide through the blood-brain barrier in the rat. Journal of Pharmacology and Experimental Therapeutics 278(1): 107-113, 1996

Concentrations of morphine, morphine-6-glucuronide and morphine-3-glucuronide in serum and cerebrospinal fluid following morphine administration to patients with morphine-resistant pain. Pain. 56(2): 145-149, 1994

Probenecid interacts with the pharmacokinetics of morphine-6 glucuronide in humans. Anesthesiology (Hagerstown) 101(6): 1394-1399, 2004

Disposition and clinical effects of morphine, morphine-6-glucuronide and morphine-3-glucuronide following an intentional overdose of slow release oral morphine in a patient with renal failure. Drug Investigation 6(5): 291-295, 1993

Determination of morphine, morphine-3-glucuronide, and morphine-6-glucuronide in plasma after intravenous and intrathecal morphine administration using HPLC with electrospray ionization and tandem mass spectrometry. Journal of Analytical Toxicology 23(6): 468-473, 1999