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Brain Uptake of Methylprednisolone Acetate: From the Cerebrospinal Fluid and Systemic Sites

Brain Uptake of Methylprednisolone Acetate: From the Cerebrospinal Fluid and Systemic Sites Abstract Tritiated-α-methylprednisolone-21-acetate was prepared in a dosage form comparable to commercial Depo-Medrol and administered to adult cats either intracisternally or intraperitoneally. Therapeutic amounts of tritiated methylprednisolone acetate were taken up rapidly from the subarachnoid space of cats into the central nervous system to reach levels five to ten times higher than could be attained by systemic injection. Plasma steroid levels were similar whether the drug was placed in the peritoneal or cisternal space. Although the steroid concentration in brain declined rapidly during the first 24 hours after intrathecal injection, steroid was still detectable seven days later. White matter regions tended to attain and retain larger amounts of steroid than gray. Brain steroid levels after intrathecal administration, probably represent a steady state between the rate of diffusion of steroid into the brain from the cerebrospinal fluid (CSF) and its rate of removal by the circulation. Provided that high CSF steroid levels are attained, higher and more prolonged therapeutic brain levels will result after intrathecal administration than by other routes. References 1. Lehrer GM, Weissbarth S, Maker HS: Brain uptake of methylprednisolone acetate from the CSF and systemic sites . Trans Am Neurol Assoc 96:268-269, 1971. 2. Goldstein NP, McKenzie BF, McGuckin WF: Changes in cerebrospinal fluid of patients with multiple sclerosis after treatment with intrathecal methylprednisolone acetate: A preliminary report . Proc Staff Mtg Mayo Clin 37:657-668, 1962. 3. Van Buskirk C, et al: Treatment of multiple sclerosis with intrathecal steroids . Neurology 14:595-597, 1964.Crossref 4. Sibley WA: Drug treatment of multiple sclerosis , in Vimkin PJ, Bruyn GW (eds): Handbook of Clinical Neurology , Amsterdam, North Holland Publishing Co, 1972, vol 13, chap 13. 5. Fishman RA, Christy NP: Fate of adrenal cortisol steroids following intrathecal injection . Neurology 15:1-6, 1965.Crossref 6. Lehrer GM, Maker HS, Weissbarth S: Brain uptake of cortisol and cortisone from the CSF and systemic sites . Neurology 23:63-69, 1973.Crossref 7. Eik-Nes KB, Brizzee KR: Concentration of tritium in brain tissue of dogs given (1,2,-3H2) cortisol intravenously . Biochim Biophys Acta 97: 320-333, 1965.Crossref 8. Monder C, Walker MC: Identification of 11β,17α-dihydroxy-3,20-dioxo-4-pregnene-21-al-1,2-3H (21-dehydrocortisol-1,2-3H) and 11β-hydroxy-4-androstene-3,17-dione-1,2-3H as contaminants in preparations of cortisol-1,2-3H . Steroids 15:1-11, 1970.Crossref 9. Silber RH, Porter CC: The determination of 17,21-dihydroxy-20-ketosteroids in urine and plasma . J Biol Chem 210:923-932, 1954. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Neurology American Medical Association

Brain Uptake of Methylprednisolone Acetate: From the Cerebrospinal Fluid and Systemic Sites

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Publisher
American Medical Association
Copyright
Copyright © 1973 American Medical Association. All Rights Reserved.
ISSN
0003-9942
eISSN
1538-3687
DOI
10.1001/archneur.1973.00490230060008
Publisher site
See Article on Publisher Site

Abstract

Abstract Tritiated-α-methylprednisolone-21-acetate was prepared in a dosage form comparable to commercial Depo-Medrol and administered to adult cats either intracisternally or intraperitoneally. Therapeutic amounts of tritiated methylprednisolone acetate were taken up rapidly from the subarachnoid space of cats into the central nervous system to reach levels five to ten times higher than could be attained by systemic injection. Plasma steroid levels were similar whether the drug was placed in the peritoneal or cisternal space. Although the steroid concentration in brain declined rapidly during the first 24 hours after intrathecal injection, steroid was still detectable seven days later. White matter regions tended to attain and retain larger amounts of steroid than gray. Brain steroid levels after intrathecal administration, probably represent a steady state between the rate of diffusion of steroid into the brain from the cerebrospinal fluid (CSF) and its rate of removal by the circulation. Provided that high CSF steroid levels are attained, higher and more prolonged therapeutic brain levels will result after intrathecal administration than by other routes. References 1. Lehrer GM, Weissbarth S, Maker HS: Brain uptake of methylprednisolone acetate from the CSF and systemic sites . Trans Am Neurol Assoc 96:268-269, 1971. 2. Goldstein NP, McKenzie BF, McGuckin WF: Changes in cerebrospinal fluid of patients with multiple sclerosis after treatment with intrathecal methylprednisolone acetate: A preliminary report . Proc Staff Mtg Mayo Clin 37:657-668, 1962. 3. Van Buskirk C, et al: Treatment of multiple sclerosis with intrathecal steroids . Neurology 14:595-597, 1964.Crossref 4. Sibley WA: Drug treatment of multiple sclerosis , in Vimkin PJ, Bruyn GW (eds): Handbook of Clinical Neurology , Amsterdam, North Holland Publishing Co, 1972, vol 13, chap 13. 5. Fishman RA, Christy NP: Fate of adrenal cortisol steroids following intrathecal injection . Neurology 15:1-6, 1965.Crossref 6. Lehrer GM, Maker HS, Weissbarth S: Brain uptake of cortisol and cortisone from the CSF and systemic sites . Neurology 23:63-69, 1973.Crossref 7. Eik-Nes KB, Brizzee KR: Concentration of tritium in brain tissue of dogs given (1,2,-3H2) cortisol intravenously . Biochim Biophys Acta 97: 320-333, 1965.Crossref 8. Monder C, Walker MC: Identification of 11β,17α-dihydroxy-3,20-dioxo-4-pregnene-21-al-1,2-3H (21-dehydrocortisol-1,2-3H) and 11β-hydroxy-4-androstene-3,17-dione-1,2-3H as contaminants in preparations of cortisol-1,2-3H . Steroids 15:1-11, 1970.Crossref 9. Silber RH, Porter CC: The determination of 17,21-dihydroxy-20-ketosteroids in urine and plasma . J Biol Chem 210:923-932, 1954.

Journal

Archives of NeurologyAmerican Medical Association

Published: May 1, 1973

References

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