التفاصيل البيبلوغرافية
| العنوان: |
Human plasma carboxylesterase and butyrylcholinesterase enzyme activity: correlations with SN-38 pharmacokinetics during a prolonged infusion of irinotecan. |
| المؤلفون: |
Guemei, Aida A., Cottrell, Jeff, Band, Roger, Hehman, Hilary, Prudhomme, Mike, Pavlov, Michael V., Grem, Jean L., Ismail, Abdel Salam, Bowen, Donnell, Taylor, Robert E., Takimoto, Chris H., Guemei, A A, Cottrell, J, Band, R, Hehman, H, Prudhomme, M, Pavlov, M V, Grem, J L, Ismail, A S, Bowen, D |
| المصدر: |
Cancer Chemotherapy & Pharmacology; Apr2001, Vol. 47 Issue 4, p283-290, 8p |
| مصطلحات موضوعية: |
CANCER patients, BUTYRYLCHOLINESTERASE, CHOLINESTERASES, PHARMACOKINETICS, CLINICAL medicine, INTRAVENOUS therapy |
| مستخلص: |
Purpose: To characterize the relationships between human plasma irinotecan carboxylesterase-converting enzyme activity, caboxylesterase-mediated hydrolysis of p-nitrophenyl acetate (pNPA), and the butyrylcholinesterase-mediated hydrolysis of butyrylthiocholine in human plasma and to test the ability of these in vitro tests to predict the variability in SN-38 pharmacokinetics in adult patients during a prolonged infusion of irinotecan.Methods: Individual plasma-converting enzyme activity was measured in 20 adult cancer patients participating in a pharmacokinetic and phase I clinical trial of a prolonged 96-h intravenous infusion of irinotecan. The pNPA and butyrylthiocholine hydrolysis in patient plasma was also assayed.Results: The irinotecan carboxylesterase-converting enzyme in human plasma had a Vmax of 89.9 +/- 22.7 pmol/h per ml plasma and a Km of 207 +/- 56 microM (mean +/- SD, n = 3). The mean value of the specific activity of this enzyme in 20 adult cancer patients was 10.08 +/- 2.96 pmol/h per ml plasma ranging from 5.43 to 15.39 pmol/h per ml. The area-under-the-concentration-versus time curve (AUC) ratio of SN-38 to irinotecan (AUCSN-38/AUCCPT-11) was used to assess the relative SN-38 exposure to the active metabolite in individual patients. Pharmacokinetic variations in the relative exposure to SN-38 did not correlate with the measured carboxylesterase-converting enzyme activity nor with plasma butyrylcholinesterase activity in our patient population. However, it did correlate with the measured pNPA hydrolysis activity in patient plasma (r2 = 0.350, P = 0.0124, n = 18).Conclusions: Determination of patient plasma pNPA hydrolysis activity may have utility in predicting SN-38 pharmacokinetics during prolonged infusions of irinotecan. [ABSTRACT FROM AUTHOR] |
|
Copyright of Cancer Chemotherapy & Pharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Find this article in full text from Springer Verlag. 
Full Text Finder