The binding of ketamine to plasma proteins: Emphasis on human plasma
| ISSN: |
1432-1041
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| Keywords: |
ketamine ; binding to plasma proteins ; alpha1-acid glycoprotein ; albumin ; pH change
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| Source: |
Springer Online Journal Archives 1860-2000
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| Topics: |
Chemistry and Pharmacology
Medicine
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| Notes: |
Summary We report for the first time that ketamine (K) is bound as much as 47% to human plasma. It was shown that binding of K to plasma and albumin is dependent on pH; binding is decreased at pH lower than 7.4 and increased at higher pH. This is in concordance with the pKa of K being 7.5; the partition coefficient between an organic phase and buffer was found to be sensitive to small pH changes. Binding of K is also influenced by albumin concentration and the affinity of K for human α1-acid glycoprotein (AAG) is much higher than for human albumin (HSA). The major metabolite nor-K does not appreciably displace K from binding sites on HSA. These findings may explain in part the variability of binding of K observed with different human samples. Human cord plasma exhibits a lower binding of K than adult plasma. This is probably the result of much lower AAG concentration in cord compared to adult plasma; cord and adult plasma albumin levels are known to be only slightly different. Since K has 2 optically active isomers, one of which is more potent than the other, experiments on the binding of racemic and the 2 isomers of K were performed; no differences in binding to AAG were found. We were, however, able to show that tris (butoxyethyl) phosphate (TBEP) can abolish binding of K to AAG. Thus the presence of TBEP would interfere in determining plasma levels and distribution of K. An example would be in the measurement of the partition of K between human red cells and plasma. We determined this ratio in human blood in the absence of TBEP and found it to be similar to that reported for dog red blood cells and plasma.
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| Type of Medium: |
Electronic Resource
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| URL: |
| _version_ | 1798295565521387520 |
|---|---|
| autor | Dayton, P. G. Stiller, R. L. Cook, D. R. Perel, J. M. |
| autorsonst | Dayton, P. G. Stiller, R. L. Cook, D. R. Perel, J. M. |
| book_url | http://dx.doi.org/10.1007/BF00607095 |
| datenlieferant | nat_lic_papers |
| hauptsatz | hsatz_simple |
| identnr | NLM202439968 |
| issn | 1432-1041 |
| journal_name | European journal of clinical pharmacology |
| materialart | 1 |
| notes | Summary We report for the first time that ketamine (K) is bound as much as 47% to human plasma. It was shown that binding of K to plasma and albumin is dependent on pH; binding is decreased at pH lower than 7.4 and increased at higher pH. This is in concordance with the pKa of K being 7.5; the partition coefficient between an organic phase and buffer was found to be sensitive to small pH changes. Binding of K is also influenced by albumin concentration and the affinity of K for human α1-acid glycoprotein (AAG) is much higher than for human albumin (HSA). The major metabolite nor-K does not appreciably displace K from binding sites on HSA. These findings may explain in part the variability of binding of K observed with different human samples. Human cord plasma exhibits a lower binding of K than adult plasma. This is probably the result of much lower AAG concentration in cord compared to adult plasma; cord and adult plasma albumin levels are known to be only slightly different. Since K has 2 optically active isomers, one of which is more potent than the other, experiments on the binding of racemic and the 2 isomers of K were performed; no differences in binding to AAG were found. We were, however, able to show that tris (butoxyethyl) phosphate (TBEP) can abolish binding of K to AAG. Thus the presence of TBEP would interfere in determining plasma levels and distribution of K. An example would be in the measurement of the partition of K between human red cells and plasma. We determined this ratio in human blood in the absence of TBEP and found it to be similar to that reported for dog red blood cells and plasma. |
| package_name | Springer |
| publikationsjahr_anzeige | 1983 |
| publikationsjahr_facette | 1983 |
| publikationsjahr_intervall | 8019:1980-1984 |
| publikationsjahr_sort | 1983 |
| publisher | Springer |
| reference | 24 (1983), S. 825-831 |
| schlagwort | ketamine binding to plasma proteins alpha1-acid glycoprotein albumin pH change |
| search_space | articles |
| shingle_author_1 | Dayton, P. G. Stiller, R. L. Cook, D. R. Perel, J. M. |
| shingle_author_2 | Dayton, P. G. Stiller, R. L. Cook, D. R. Perel, J. M. |
| shingle_author_3 | Dayton, P. G. Stiller, R. L. Cook, D. R. Perel, J. M. |
| shingle_author_4 | Dayton, P. G. Stiller, R. L. Cook, D. R. Perel, J. M. |
| shingle_catch_all_1 | Dayton, P. G. Stiller, R. L. Cook, D. R. Perel, J. M. The binding of ketamine to plasma proteins: Emphasis on human plasma ketamine binding to plasma proteins alpha1-acid glycoprotein albumin pH change ketamine binding to plasma proteins alpha1-acid glycoprotein albumin pH change Summary We report for the first time that ketamine (K) is bound as much as 47% to human plasma. It was shown that binding of K to plasma and albumin is dependent on pH; binding is decreased at pH lower than 7.4 and increased at higher pH. This is in concordance with the pKa of K being 7.5; the partition coefficient between an organic phase and buffer was found to be sensitive to small pH changes. Binding of K is also influenced by albumin concentration and the affinity of K for human α1-acid glycoprotein (AAG) is much higher than for human albumin (HSA). The major metabolite nor-K does not appreciably displace K from binding sites on HSA. These findings may explain in part the variability of binding of K observed with different human samples. Human cord plasma exhibits a lower binding of K than adult plasma. This is probably the result of much lower AAG concentration in cord compared to adult plasma; cord and adult plasma albumin levels are known to be only slightly different. Since K has 2 optically active isomers, one of which is more potent than the other, experiments on the binding of racemic and the 2 isomers of K were performed; no differences in binding to AAG were found. We were, however, able to show that tris (butoxyethyl) phosphate (TBEP) can abolish binding of K to AAG. Thus the presence of TBEP would interfere in determining plasma levels and distribution of K. An example would be in the measurement of the partition of K between human red cells and plasma. We determined this ratio in human blood in the absence of TBEP and found it to be similar to that reported for dog red blood cells and plasma. 1432-1041 14321041 Springer |
| shingle_catch_all_2 | Dayton, P. G. Stiller, R. L. Cook, D. R. Perel, J. M. The binding of ketamine to plasma proteins: Emphasis on human plasma ketamine binding to plasma proteins alpha1-acid glycoprotein albumin pH change ketamine binding to plasma proteins alpha1-acid glycoprotein albumin pH change Summary We report for the first time that ketamine (K) is bound as much as 47% to human plasma. It was shown that binding of K to plasma and albumin is dependent on pH; binding is decreased at pH lower than 7.4 and increased at higher pH. This is in concordance with the pKa of K being 7.5; the partition coefficient between an organic phase and buffer was found to be sensitive to small pH changes. Binding of K is also influenced by albumin concentration and the affinity of K for human α1-acid glycoprotein (AAG) is much higher than for human albumin (HSA). The major metabolite nor-K does not appreciably displace K from binding sites on HSA. These findings may explain in part the variability of binding of K observed with different human samples. Human cord plasma exhibits a lower binding of K than adult plasma. This is probably the result of much lower AAG concentration in cord compared to adult plasma; cord and adult plasma albumin levels are known to be only slightly different. Since K has 2 optically active isomers, one of which is more potent than the other, experiments on the binding of racemic and the 2 isomers of K were performed; no differences in binding to AAG were found. We were, however, able to show that tris (butoxyethyl) phosphate (TBEP) can abolish binding of K to AAG. Thus the presence of TBEP would interfere in determining plasma levels and distribution of K. An example would be in the measurement of the partition of K between human red cells and plasma. We determined this ratio in human blood in the absence of TBEP and found it to be similar to that reported for dog red blood cells and plasma. 1432-1041 14321041 Springer |
| shingle_catch_all_3 | Dayton, P. G. Stiller, R. L. Cook, D. R. Perel, J. M. The binding of ketamine to plasma proteins: Emphasis on human plasma ketamine binding to plasma proteins alpha1-acid glycoprotein albumin pH change ketamine binding to plasma proteins alpha1-acid glycoprotein albumin pH change Summary We report for the first time that ketamine (K) is bound as much as 47% to human plasma. It was shown that binding of K to plasma and albumin is dependent on pH; binding is decreased at pH lower than 7.4 and increased at higher pH. This is in concordance with the pKa of K being 7.5; the partition coefficient between an organic phase and buffer was found to be sensitive to small pH changes. Binding of K is also influenced by albumin concentration and the affinity of K for human α1-acid glycoprotein (AAG) is much higher than for human albumin (HSA). The major metabolite nor-K does not appreciably displace K from binding sites on HSA. These findings may explain in part the variability of binding of K observed with different human samples. Human cord plasma exhibits a lower binding of K than adult plasma. This is probably the result of much lower AAG concentration in cord compared to adult plasma; cord and adult plasma albumin levels are known to be only slightly different. Since K has 2 optically active isomers, one of which is more potent than the other, experiments on the binding of racemic and the 2 isomers of K were performed; no differences in binding to AAG were found. We were, however, able to show that tris (butoxyethyl) phosphate (TBEP) can abolish binding of K to AAG. Thus the presence of TBEP would interfere in determining plasma levels and distribution of K. An example would be in the measurement of the partition of K between human red cells and plasma. We determined this ratio in human blood in the absence of TBEP and found it to be similar to that reported for dog red blood cells and plasma. 1432-1041 14321041 Springer |
| shingle_catch_all_4 | Dayton, P. G. Stiller, R. L. Cook, D. R. Perel, J. M. The binding of ketamine to plasma proteins: Emphasis on human plasma ketamine binding to plasma proteins alpha1-acid glycoprotein albumin pH change ketamine binding to plasma proteins alpha1-acid glycoprotein albumin pH change Summary We report for the first time that ketamine (K) is bound as much as 47% to human plasma. It was shown that binding of K to plasma and albumin is dependent on pH; binding is decreased at pH lower than 7.4 and increased at higher pH. This is in concordance with the pKa of K being 7.5; the partition coefficient between an organic phase and buffer was found to be sensitive to small pH changes. Binding of K is also influenced by albumin concentration and the affinity of K for human α1-acid glycoprotein (AAG) is much higher than for human albumin (HSA). The major metabolite nor-K does not appreciably displace K from binding sites on HSA. These findings may explain in part the variability of binding of K observed with different human samples. Human cord plasma exhibits a lower binding of K than adult plasma. This is probably the result of much lower AAG concentration in cord compared to adult plasma; cord and adult plasma albumin levels are known to be only slightly different. Since K has 2 optically active isomers, one of which is more potent than the other, experiments on the binding of racemic and the 2 isomers of K were performed; no differences in binding to AAG were found. We were, however, able to show that tris (butoxyethyl) phosphate (TBEP) can abolish binding of K to AAG. Thus the presence of TBEP would interfere in determining plasma levels and distribution of K. An example would be in the measurement of the partition of K between human red cells and plasma. We determined this ratio in human blood in the absence of TBEP and found it to be similar to that reported for dog red blood cells and plasma. 1432-1041 14321041 Springer |
| shingle_title_1 | The binding of ketamine to plasma proteins: Emphasis on human plasma |
| shingle_title_2 | The binding of ketamine to plasma proteins: Emphasis on human plasma |
| shingle_title_3 | The binding of ketamine to plasma proteins: Emphasis on human plasma |
| shingle_title_4 | The binding of ketamine to plasma proteins: Emphasis on human plasma |
| sigel_instance_filter | dkfz geomar wilbert ipn albert fhp |
| source_archive | Springer Online Journal Archives 1860-2000 |
| timestamp | 2024-05-06T09:38:13.876Z |
| titel | The binding of ketamine to plasma proteins: Emphasis on human plasma |
| titel_suche | The binding of ketamine to plasma proteins: Emphasis on human plasma |
| topic | V WW-YZ |
| uid | nat_lic_papers_NLM202439968 |