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Altered brain exposure of morphine in experimental meningitis studied with microdialysis

Tunblad, K; Ederoth, Per LU ; Gärdenfors, Anna LU ; Hammarlund-Udenaes, M and Nordström, Carl-Henrik LU (2004) In Acta Anaesthesiologica Scandinavica 48(3). p.294-301
Abstract
Background: During pathologic conditions such as meningitis and traumatic brain injury the function of the blood-brain barrier (BBB) is disturbed. In the present study we examined the cerebral pharmacokinetic pattern of morphine in the intact brain and during experimentally induced meningitis using a pig model. Secondly, the use of intracerebral microdialysis as a potential tool for monitoring damage in the BBB by studying the pharmacokinetics of morphine is addressed. Methods: Six pigs were studied under general anaesthesia. One occipital and two frontal microdialysis probes and one pressure transducer were inserted into the brain tissue. Another probe was placed into the jugularis interna. Morphine 1 mg kg(-1) was administered as a... (More)
Background: During pathologic conditions such as meningitis and traumatic brain injury the function of the blood-brain barrier (BBB) is disturbed. In the present study we examined the cerebral pharmacokinetic pattern of morphine in the intact brain and during experimentally induced meningitis using a pig model. Secondly, the use of intracerebral microdialysis as a potential tool for monitoring damage in the BBB by studying the pharmacokinetics of morphine is addressed. Methods: Six pigs were studied under general anaesthesia. One occipital and two frontal microdialysis probes and one pressure transducer were inserted into the brain tissue. Another probe was placed into the jugularis interna. Morphine 1 mg kg(-1) was administered as a 10-min infusion, and morphine concentrations were then measured for 3 h. Meningitis was subsequently induced by injecting lipopolysaccharide into the cisterna magna. When meningitis was established, the morphine experiment was repeated. Results: The unbound area under the concentration-time curve (AUC(u)) ratio of morphine in brain to blood was 0.47 (0.19) during the control period, and 0.95 (0.20) (P<0.001) during meningitis. The increase in the brain/blood AUC(u) ratio during meningitis implies decreased active efflux and increased passive diffusion of morphine over the BBB. The half-life of morphine in brain was longer than in blood during both periods, and was unaffected by meningitis. Conclusion: This study demonstrates that the morphine exposure to the brain is significantly increased during meningitis as compared with the control situation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
microdialysis, meningitis, drug transport, blood-brain barrier, disease states, morphine, pharmacokinetics and pig
in
Acta Anaesthesiologica Scandinavica
volume
48
issue
3
pages
294 - 301
publisher
Wiley-Blackwell
external identifiers
  • wos:000220251400005
  • pmid:14982561
  • scopus:1542316787
ISSN
0001-5172
DOI
10.1111/j.0001-5172.2003.0311.x
language
English
LU publication?
yes
id
953d9136-0a3d-426e-b638-918b5b03d693 (old id 285009)
date added to LUP
2007-11-03 10:45:53
date last changed
2017-09-03 03:50:45
@article{953d9136-0a3d-426e-b638-918b5b03d693,
  abstract     = {Background: During pathologic conditions such as meningitis and traumatic brain injury the function of the blood-brain barrier (BBB) is disturbed. In the present study we examined the cerebral pharmacokinetic pattern of morphine in the intact brain and during experimentally induced meningitis using a pig model. Secondly, the use of intracerebral microdialysis as a potential tool for monitoring damage in the BBB by studying the pharmacokinetics of morphine is addressed. Methods: Six pigs were studied under general anaesthesia. One occipital and two frontal microdialysis probes and one pressure transducer were inserted into the brain tissue. Another probe was placed into the jugularis interna. Morphine 1 mg kg(-1) was administered as a 10-min infusion, and morphine concentrations were then measured for 3 h. Meningitis was subsequently induced by injecting lipopolysaccharide into the cisterna magna. When meningitis was established, the morphine experiment was repeated. Results: The unbound area under the concentration-time curve (AUC(u)) ratio of morphine in brain to blood was 0.47 (0.19) during the control period, and 0.95 (0.20) (P&lt;0.001) during meningitis. The increase in the brain/blood AUC(u) ratio during meningitis implies decreased active efflux and increased passive diffusion of morphine over the BBB. The half-life of morphine in brain was longer than in blood during both periods, and was unaffected by meningitis. Conclusion: This study demonstrates that the morphine exposure to the brain is significantly increased during meningitis as compared with the control situation.},
  author       = {Tunblad, K and Ederoth, Per and Gärdenfors, Anna and Hammarlund-Udenaes, M and Nordström, Carl-Henrik},
  issn         = {0001-5172},
  keyword      = {microdialysis,meningitis,drug transport,blood-brain barrier,disease states,morphine,pharmacokinetics and pig},
  language     = {eng},
  number       = {3},
  pages        = {294--301},
  publisher    = {Wiley-Blackwell},
  series       = {Acta Anaesthesiologica Scandinavica},
  title        = {Altered brain exposure of morphine in experimental meningitis studied with microdialysis},
  url          = {http://dx.doi.org/10.1111/j.0001-5172.2003.0311.x},
  volume       = {48},
  year         = {2004},
}