Altered brain exposure of morphine in experimental meningitis studied with microdialysis

• 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Anestesi och intensivvård (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Anesthesiology and Intensive Care (hsv//eng)

Keyword

microdialysis

meningitis

drug transport

blood-brain barrier

disease states

morphine

pharmacokinetics and pig

Publication and Content Type

art (subject category)

ref (subject category)