Prediction of hepatic microsomal intrinsic clearance and human clearance values for drugs
Само за регистроване кориснике
2009
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Twenty-nine drugs of different structures were used in theoretical QSAR analysis of human hepatic microsomal intrinsic clearance (in vitro T(1/2) and in vitro CL(int)') and whole body clearance (CL(blood)). The examined compounds demonstrated a wide range of scaled intrinsic clearance values. Constitutional, geometrical, physico-chemical and electronic descriptors were computed for the examined structures by use of the Marvin Sketch 5.1.3_2, the Chem3D Ultra 7.0.0 and the Dragon 5.4 program. Partial least squares regression (PLSR), has been applied for selection of the most relevant molecular descriptors and development of quantitative structure-activity relatioship (QSAR) model for human hepatic microsomal intrinsic clearance (in vitro T(1/2)). Optimal QSAR models with nine and ten variables, R(2) > 0.808 and cross-validation parameter q(pre)(2) > 0.623, were selected and compared. Since the microsomal in vitro T(1/2) data can be used for calculation of in vitro CL(int)' and in vivo C...L(blood), the developed QSAR model will enable one to analyze the kinetics of cytochrome P450-mediated reactions in term of intrinsic clearance and whole body clearance. A comparison is made between predictions produced from the QSAR analysis and experimental data, and there appears to be generally satisfactory correlations with the literature values for intrinsic clearance data.
Кључне речи:
QSAR / Hepatic clearance / Human clearance / Drug metabolism / Cytochrome P450 enzymeИзвор:
Journal of Molecular Graphics & Modelling, 2009, 28, 3, 245-252Издавач:
- Elsevier Science Inc, New York
Финансирање / пројекти:
- Синтеза, квантитативни односи између структуре/особина и активности, физичко-хемијска карактеризација и анализа фармаколошки активних супстанци (RS-MESTD-MPN2006-2010-142071)
DOI: 10.1016/j.jmgm.2009.08.002
ISSN: 1093-3263
PubMed: 19713138
WoS: 000271349300005
Scopus: 2-s2.0-70349584738
Институција/група
PharmacyTY - JOUR AU - Nikolić, Katarina AU - Agbaba, Danica PY - 2009 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1200 AB - Twenty-nine drugs of different structures were used in theoretical QSAR analysis of human hepatic microsomal intrinsic clearance (in vitro T(1/2) and in vitro CL(int)') and whole body clearance (CL(blood)). The examined compounds demonstrated a wide range of scaled intrinsic clearance values. Constitutional, geometrical, physico-chemical and electronic descriptors were computed for the examined structures by use of the Marvin Sketch 5.1.3_2, the Chem3D Ultra 7.0.0 and the Dragon 5.4 program. Partial least squares regression (PLSR), has been applied for selection of the most relevant molecular descriptors and development of quantitative structure-activity relatioship (QSAR) model for human hepatic microsomal intrinsic clearance (in vitro T(1/2)). Optimal QSAR models with nine and ten variables, R(2) > 0.808 and cross-validation parameter q(pre)(2) > 0.623, were selected and compared. Since the microsomal in vitro T(1/2) data can be used for calculation of in vitro CL(int)' and in vivo CL(blood), the developed QSAR model will enable one to analyze the kinetics of cytochrome P450-mediated reactions in term of intrinsic clearance and whole body clearance. A comparison is made between predictions produced from the QSAR analysis and experimental data, and there appears to be generally satisfactory correlations with the literature values for intrinsic clearance data. PB - Elsevier Science Inc, New York T2 - Journal of Molecular Graphics & Modelling T1 - Prediction of hepatic microsomal intrinsic clearance and human clearance values for drugs VL - 28 IS - 3 SP - 245 EP - 252 DO - 10.1016/j.jmgm.2009.08.002 ER -
@article{ author = "Nikolić, Katarina and Agbaba, Danica", year = "2009", abstract = "Twenty-nine drugs of different structures were used in theoretical QSAR analysis of human hepatic microsomal intrinsic clearance (in vitro T(1/2) and in vitro CL(int)') and whole body clearance (CL(blood)). The examined compounds demonstrated a wide range of scaled intrinsic clearance values. Constitutional, geometrical, physico-chemical and electronic descriptors were computed for the examined structures by use of the Marvin Sketch 5.1.3_2, the Chem3D Ultra 7.0.0 and the Dragon 5.4 program. Partial least squares regression (PLSR), has been applied for selection of the most relevant molecular descriptors and development of quantitative structure-activity relatioship (QSAR) model for human hepatic microsomal intrinsic clearance (in vitro T(1/2)). Optimal QSAR models with nine and ten variables, R(2) > 0.808 and cross-validation parameter q(pre)(2) > 0.623, were selected and compared. Since the microsomal in vitro T(1/2) data can be used for calculation of in vitro CL(int)' and in vivo CL(blood), the developed QSAR model will enable one to analyze the kinetics of cytochrome P450-mediated reactions in term of intrinsic clearance and whole body clearance. A comparison is made between predictions produced from the QSAR analysis and experimental data, and there appears to be generally satisfactory correlations with the literature values for intrinsic clearance data.", publisher = "Elsevier Science Inc, New York", journal = "Journal of Molecular Graphics & Modelling", title = "Prediction of hepatic microsomal intrinsic clearance and human clearance values for drugs", volume = "28", number = "3", pages = "245-252", doi = "10.1016/j.jmgm.2009.08.002" }
Nikolić, K.,& Agbaba, D.. (2009). Prediction of hepatic microsomal intrinsic clearance and human clearance values for drugs. in Journal of Molecular Graphics & Modelling Elsevier Science Inc, New York., 28(3), 245-252. https://doi.org/10.1016/j.jmgm.2009.08.002
Nikolić K, Agbaba D. Prediction of hepatic microsomal intrinsic clearance and human clearance values for drugs. in Journal of Molecular Graphics & Modelling. 2009;28(3):245-252. doi:10.1016/j.jmgm.2009.08.002 .
Nikolić, Katarina, Agbaba, Danica, "Prediction of hepatic microsomal intrinsic clearance and human clearance values for drugs" in Journal of Molecular Graphics & Modelling, 28, no. 3 (2009):245-252, https://doi.org/10.1016/j.jmgm.2009.08.002 . .