Abstract：
:A liposomal formulation of methylprednisolone (L-MPL) was developed to improve localization of this immunosuppressant in lymphatic tissues. Liposomes containing MPL were formulated from a mixture of phosphatydylcholine and phosphatydylglycerol (molar ratio, 9:1) and sized by extrusion through a 0.1-micron membrane. Male Sprague-Dawley rats received a bolus dose of 2 mg/kg of L-MPL or free MPL in solution (control). Samples of blood, spleen, liver, thymus, and bone marrow were collected at intervals over a 66-hr period. Concentrations of MPL in plasma and organs and free cytosolic glucocorticoid receptors (GCR) in spleen and liver were determined. The plasma MPL profiles for free and L-MPL were bi- and triexponential. Although the alpha phase kinetics of both dosage forms were similar, L-MPL showed a substantially slower elimination phase than did free drug. Incorporation of MPL into liposomes caused the following increases: terminal half-life, from 0.48 (MPL) to 30.13 hr (L-MPL); MRT, from 0.42 to 11.95 hr, Vss, from 2.10 to 21.87 L/kg; and AUC, from 339 to 1093 ng x hr/mL. Uptake of liposomes enhanced significantly the delivery of drug to lymphatic tissues and liver; AUC tissue:plasma ratios for spleen increased 77-fold; for liver, 9-fold; and for thymus, 27-fold. The duration of GCR occupancy was extended 10-fold in spleen and 13-fold in liver by the liposomal formulation. Lymphatic tissue selectivity and extended receptor binding of liposome-delivered MPL offer promise for enhanced immunosuppression.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Mishina EV,Straubinger RM,Pyszczynski NA,Jusko WJdoi
10.1023/a:1018954704886subject
Has Abstractpub_date
1993-10-01 00:00:00pages
1402-10issue
10eissn
0724-8741issn
1573-904Xjournal_volume
10pub_type
杂志文章abstract：:Physiologically-based pharmacokinetic (PBPK) models explicitly incorporate tissue-specific blood flows, partition coefficients, and metabolic processes. Since PBPK models are derived using physiologic parameters and interactions of the compound with tissue components, these models are considered to be "bottom up" as o...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
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更新日期：1995-11-01 00:00:00
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更新日期：2006-06-01 00:00:00
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更新日期：2003-02-01 00:00:00
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pub_type： 杂志文章
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更新日期：2020-01-08 00:00:00
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更新日期：2002-01-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：1995-09-01 00:00:00
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更新日期：1987-10-01 00:00:00
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pub_type： 杂志文章
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更新日期：2018-09-06 00:00:00
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更新日期：1991-09-01 00:00:00
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更新日期：2005-01-01 00:00:00
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更新日期：2020-01-02 00:00:00
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更新日期：2001-05-01 00:00:00
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更新日期：2003-01-01 00:00:00
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更新日期：2012-11-01 00:00:00
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更新日期：1990-10-01 00:00:00
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更新日期：2016-01-01 00:00:00
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journal_title：Pharmaceutical research
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更新日期：1989-01-01 00:00:00
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更新日期：2019-12-17 00:00:00
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更新日期：2018-08-09 00:00:00
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journal_title：Pharmaceutical research
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更新日期：1995-07-01 00:00:00
