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  • 1
    ISSN: 1573-904X
    Keywords: mepitiostane ; superlipophilicity ; lymph–blood partition ratio ; dynamic partitioning model ; chylomicron
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The partition of mepitiostane, testosterone, and some structurally related compounds between lymph and blood in rat jejunum (lymph–blood partition ratio; LBPR) was determined, and the quantitative relationship between LBPR and lipophilicity was examined. When the ΔR m values (hydrophobic parameter derived from the mobility) relative to testosterone were 〈0.2, their logLBPRs remained approximately constant in the range of −2 to −3. When the ΔR m values of the compounds were 〉0.2, a linear correlation (r = 0.986, n = 8) was observed between these values and the logLBPRs. The LBPR, but not the extent of lymphatic absorption, of lipophilic molecules was determined strictly by the superlipophilicity, and for high partitioning into the lymph (〉50% of the absorbed amount), the ΔR m value had to be 〉0.50 (5.65 as the logP value). The relationship between LBPR and superlipophilicity could be explained on the basis of the theoretical equations derived from absorption kinetics based on a dynamic partitioning model.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 12 (1995), S. 1333-1337 
    ISSN: 1573-904X
    Keywords: dissolution ; correlation ; convolution ; multiple unit ; enteric-coated granules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To establish the evaluating method for drug dissolution profiles in the gastrointestinal (GI) tract based on in vitro data for the enteric-coated multiple unit. Methods. Dissolution profile in the GI tract was calculated by the convolution procedure using an in vitro dissolution profile as a weighting function, and the gastric-emptying (GE) process as an input function (GE-convolution method). A computer program, GECONV, was developed for numerical execution of the convolution integral. Results. The in vivo dissolution profile of enteric-coated aspirin granules estimated by GE-convolution was in good agreement with the in vivo cumulative absorption profile calculated by the Wagner-Nelson method using the plasma concentration data after oral administration to healthy subjects. The in vitro/in vivo correlation improved markedly by taking the GE process into consideration. Conclusions. These findings indicated that this convolution method is useful for estimating the in vivo dissolution profile of drugs, when they are administered in an enteric-coated multiple unit type dosage form, because the gastric emptying process is a determinant process for the in vivo drug dissolution.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-904X
    Keywords: mepitiostane ; intrinsic lymphatic partition rate ; intestinal lymphatics ; portal absorption ; epitiostanol ; oleic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Mepitiostane (MP), epitiostanol (EP), and oleic acid were administered to the jejunal loop of mesenteric vein- and thoracic duct-cannulated rats, and the intrinsic lymphatic partition rate (ILPR) of the absorbed compounds was directly determined. When 14C-EP was administered to the jejunal loop, recovery of unchanged EP in the mesenteric blood and the lymph was 7.9 and 0.03% of the administered dose, respectively. In contrast, following administration of 14C-MP, recovery of unchanged MP in the mesenteric blood and the lymph was 1.2 and 15.0%, respectively. Thus, following passage through the mucosal cell, 99.6% of the unchanged EP was partitioned into the blood and 0.4% into the lymph, while for unchanged MP, 7.6% was partitioned into the blood and 92.4% into the lymph. When 14C-oleic acid was administered to the jejunal loop, most of the penetrating oleic acid was incorporated into triglycerides in epithelial cells and transferred exclusively into the lymph. However, of the unchanged oleic acid, only 37.6% was partitioned into the lymph and 62.4% into the blood. The ILPR was 92.4% for MP, 0.4% for EP, and 37.6% for oleic acid. We conclude that the ILPR values indicate the true lymphotropic property of the compounds.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 9 (1992), S. 1617-1621 
    ISSN: 1573-904X
    Keywords: mepitiostane ; epitiostanol ; intrinsic lymphatic partition rate ; lipophilicity ; chylomicron
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Substitution of the steroid epitiostanol (EP) at position 17 with methoxycyclopentane yields the extremely lipophilic mepitiostane (MP) with preferential partitioning into the lymph. Most of the MP in the lymph was associated with the core lipids of chylomicrons and very low-density lipoproteins (VLDL), as was also the case for EP. However, the dialysis velocity of EP and MP from lymph to plasma differed greatly; EP, but not MP, was transferred from the lymph to the plasma. This difference was attributed to differences in their unbound fraction in the lymph. Lymphatic transfer and the logP value of several tested steroids correlated well. Therefore, the oral EP prodrug, MP, partitioned into the lymph because of its superlipophilicity and resultant retention in the core lipids of chylomicrons and VLDL.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Biomedical Chromatography 8 (1994), S. 9-13 
    ISSN: 0269-3879
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: This paper describes a method suitable for purifying immunotoxin containing type 1 ribosome-inactivating protein, gelonin. The separation of free (unreacted) 80G, a monoclonal antibody against α-fetoprotein (AFP), from semipurified 80G-gelonin conjugate was unsuccessful by conventional CM-Sepharose ion-exchange chromatography because the isoelectric point of the conjugate did not increase enough to reach that of gelonin alone. In contrast, Blue Sepharose affinity chromatography could efficiently separate free 80G from the semipurified conjugate because the conjugate was bound to the column by its gelonin moiety while free 80G was not in buffer containing NaCl of a particular concentration range. However, a small amount of conjugate containing gelonin modified with N-succinimidyl 3-(2-pyridyldithio)propionate, but not with 2-iminothiolane, could not bind to the column. The conjugate purified by the use of Blue Sepharose showed selective cytotoxicity against AFP-producing human hepatoma cells.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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