A novel method using nuclear magnetic resonance for plasma protein binding assessment in drug discovery programs

被引：15

作者：

Gallo, Mariana ^{[1
]}

Matteucci, Sara ^{[2
]}

Alaimo, Nadine ^{[2
]}

Pitti, Erica ^{[2
]}

Orsale, Maria, V ^{[1
]}

Summa, Vincenzo ^{[1
]}

Cicero, Daniel O. ^{[1
,2
]}

Monteagudo, Edith ^{[1
]}

机构：

[1] IRBM Sci Pk SpA, Via Pontina Km 30-600, I-00071 Rome, Italy

[2] Univ Roma Tor Vergata, Dipartimento Sci & Tecnol Chim, Via Ric Sci, I-00133 Rome, Italy

来源：

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS | 2019年 / 167卷

关键词：

Plasma protein binding; NMR; Protein-ligand interaction; Drug discovery; Screening; CLINICAL PHARMACOKINETICS; ALPHA-1-ACID GLYCOPROTEIN; ZIDOVUDINE; VERAPAMIL; KINETICS;

D O I：

10.1016/j.jpba.2019.01.049

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

A new methodology based on Nuclear Magnetic Resonance (NMR) was developed to determine plasma protein binding (PPB) of drug candidates in drug discovery programs. A strong correlation was found between the attenuation of NMR signals of diverse drugs in the presence of different plasma concentrations and their fraction bound (f(b)) reported in the literature. Based on these results, a protocol for a rapid calculation of fb of small molecules was established. The advantage of using plasma instead of purified recombinant proteins and the possibility of pool analysis to increase throughput were also evaluated. This novel methodology proved to be very versatile, cost-effective, fast and suitable for automation. As a plus, it contemporarily provides a quality check and solubility of the compound. (C) 2019 The Authors. Published by Elsevier B.V.

引用

页码：21 / 29

页数：9

共 37 条

[21] Pharmacokinetics, protein binding, and tissue distribution of orally administered cefpodoxime proxetil and cephalexin in dogs
Papich, Mark G.
Davis, Jennifer L.
Floerchinger, Amanda M.
[J]. AMERICAN JOURNAL OF VETERINARY RESEARCH, 2010, 71 (12) : 1484 - 1491
[22] Analysis of the interaction between alpha-1-acid glycoprotein and tamoxifen and its metabolites
Paterson, SC
Lim, CK
Smith, KD
[J]. BIOMEDICAL CHROMATOGRAPHY, 2003, 17 (2-3) : 143 - 148
[23] Ramasubramaniyan P., 2015, WORLD J PHARM PHARM, V4, P1361
[24] CLINICAL PHARMACOKINETICS OF RANITIDINE
ROBERTS, CJC
[J]. CLINICAL PHARMACOKINETICS, 1984, 9 (03) : 211 - 221
[25] PROTEIN-BINDING OF ZIDOVUDINE IN THE SERA OF HEALTHY CONTROLS AND PATIENTS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS
ROLINSKI, B
WINTERGERST, U
SADRI, I
BOGNER, JR
GOEBEL, FD
ROSCHER, A
BELOHRADSKY, BH
[J]. DRUG INVESTIGATION, 1993, 5 (03): : 166 - 172
[26] Schoetensack W., 1983, NEW DRUGS ANN CARDIO, P19
[27] SCHROEDER DH, 1983, J CLIN PSYCHIAT, V44, P79
[28] Seyffart G., 2012, DRUG DOSAGE RENAL IN, P115
[29] Estimating Protein-Ligand Binding Affinity Using High-Throughput Screening by NMR
Shortridge, Matthew D.
Hage, David S.
Harbison, Gerard S.
Powers, Robert
[J]. JOURNAL OF COMBINATORIAL CHEMISTRY, 2008, 10 (06): : 948 - 958
[30] Singh J.K., 2012, J BIOEQUIVALENCE BIO, DOI [10.4172/jbb.S14-005, DOI 10.4172/JBB.S14-005]

← 1 2 3 4 →