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Article: Histone deacetylase inhibitor enhances the anti-leukemic activity of an established nucleoside analogue.

Acharya, Milin R / Figg, William D

2004 Volume 3, Issue 8, Page(s) 719–720

Abstract: Interest in histone deacetylase (HDAC) inhibitors as antineoplastic agents has been accelerating over the last several years and increasing number of compounds are in or entering clinical trials in humans. Recently, attention has been focused on the ... ...

Abstract	Interest in histone deacetylase (HDAC) inhibitors as antineoplastic agents has been accelerating over the last several years and increasing number of compounds are in or entering clinical trials in humans. Recently, attention has been focused on the ability of HDAC inhibitors to induce perturbations in cell cycle regulatory proteins (e.g. p21CIP1), down regulation of survival signaling pathways (e.g. Raf/MAPkinase/ERK), and disruption of cellular redox state (e.g. reactive oxygen species, ROS). In April 2004 issue of Cancer Research, Maggio et al. report that pre-treatment of human leukemic cells with a histone deacetylase inhibitor, MS-275 significantly enhances the abrogative capacity of an established nucleoside analogue, fludarabine. The study indicates that apart from promoting acetylation of histones and regulation of genes involved in differentiation and apoptosis, MS-275 also induces multiple perturbations in signal transduction, survival and cell cycle regulatory pathways that increase the fludarabine-mediated cell death.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Apoptosis/drug effects ; Benzamides/therapeutic use ; Cell Cycle/drug effects ; Cell Cycle Proteins/metabolism ; DNA (Cytosine-5-)-Methyltransferases/antagonists & inhibitors ; Drug Synergism ; Enzyme Activation/drug effects ; Enzyme Inhibitors/pharmacology ; Histone Deacetylase Inhibitors ; Histones/metabolism ; Humans ; Leukemia/drug therapy ; Leukemia/metabolism ; Pyridines/therapeutic use ; Reactive Oxygen Species/metabolism ; Vidarabine/analogs & derivatives ; Vidarabine/therapeutic use
Chemical Substances	Antineoplastic Agents ; Benzamides ; Cell Cycle Proteins ; Enzyme Inhibitors ; Histone Deacetylase Inhibitors ; Histones ; Pyridines ; Reactive Oxygen Species ; entinostat (1ZNY4FKK9H) ; DNA (Cytosine-5-)-Methyltransferases (EC 2.1.1.37) ; Vidarabine (FA2DM6879K) ; fludarabine (P2K93U8740)
Language	English
Publishing date	2004-08-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2146305-0
ISSN	1538-4047
ISSN	1538-4047
DOI	10.4161/cbt.3.8.1065
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Article: Rational development of histone deacetylase inhibitors as anticancer agents: a review.

Acharya, Milin R / Sparreboom, Alex / Venitz, Jürgen / Figg, William D

Molecular pharmacology

2005 Volume 68, Issue 4, Page(s) 917–932

Abstract: The epigenome is defined by DNA methylation patterns and the associated post-translational modifications of histones. This histone code determines the expression status of individual genes dependent upon their localization on the chromatin. The histone ... ...

Abstract	The epigenome is defined by DNA methylation patterns and the associated post-translational modifications of histones. This histone code determines the expression status of individual genes dependent upon their localization on the chromatin. The histone deacetylases (HDACs) play a major role in keeping the balance between the acetylated and deacetylated states of chromatin and eventually regulate gene expression. Recent developments in understanding the cancer cell cycle, specifically the interplay with chromatin control, are providing opportunities for developing mechanism-based therapeutic drugs. Inhibitors of HDACs are under considerable exploration, in part because of their potential roles in reversing the silenced genes in transformed tumor cells by modulating transcriptional processes. This review is an effort to summarize the nonclinical and clinical status of HDAC inhibitors currently under development in anticancer therapy.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Drug Design ; Enzyme Inhibitors/pharmacology ; Histone Deacetylase Inhibitors ; Humans
Chemical Substances	Antineoplastic Agents ; Enzyme Inhibitors ; Histone Deacetylase Inhibitors
Language	English
Publishing date	2005-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	124034-1
ISSN	1521-0111 ; 0026-895X
ISSN (online)	1521-0111
ISSN	0026-895X
DOI	10.1124/mol.105.014167
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Zs.A 525: Show issues

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Article: Herbal remedies in the United States: potential adverse interactions with anticancer agents.

Sparreboom, Alex / Cox, Michael C / Acharya, Milin R / Figg, William D

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2004 Volume 22, Issue 12, Page(s) 2489–2503

Abstract: Purpose: Interest in the use of herbal products has grown dramatically in the Western world. Recent estimates suggest an overall prevalence for herbal preparation use of 13% to 63% among cancer patients. With the narrow therapeutic range associated with ...

Abstract	Purpose: Interest in the use of herbal products has grown dramatically in the Western world. Recent estimates suggest an overall prevalence for herbal preparation use of 13% to 63% among cancer patients. With the narrow therapeutic range associated with most anticancer drugs, there is an increasing need for understanding possible adverse drug interactions in medical oncology. Methods: In this article, a literature overview is provided of known or suspected interactions of the 15 best-selling herbs in the United States with conventional allopathic therapies for cancer. Results: Herbs with the potential to significantly modulate the activity of drug-metabolizing enzymes (notably cytochrome p450 isozymes) and/or the drug transporter P-glycoprotein include garlic (Allium sativum), ginkgo (Ginkgo biloba), echinacea (Echinacea purpurea), ginseng (Panax ginseng), St John' s wort (Hypericum perforatum), and kava (Piper methysticum). All of these products participate in potential pharmacokinetic interactions with anticancer drugs. Conclusion: It is suggested that health care professionals and consumers should be aware of the potential for adverse interactions with these herbs, question their patients on their use of them, especially among patients whose disease is not responding to treatments as expected, and urge patients to avoid herbs that could confound their cancer care.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Dietary Supplements/adverse effects ; Herb-Drug Interactions ; Humans ; Plant Preparations/adverse effects ; United States
Chemical Substances	Antineoplastic Agents ; Plant Preparations
Language	English
Publishing date	2004-06-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.2004.08.182
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Zs.A 1847: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Chemically modified tetracyclines as inhibitors of matrix metalloproteinases.

Acharya, Milin R / Venitz, Jürgen / Figg, William D / Sparreboom, Alex

Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy

2004 Volume 7, Issue 3, Page(s) 195–208

Abstract: Matrix metalloproteinases belong to a diverse group of enzymes that are not only involved in restructuring the extracellular matrix, but also play a major role in various pathophysiological conditions by virtue of their complicated expression, activation, ...

Abstract	Matrix metalloproteinases belong to a diverse group of enzymes that are not only involved in restructuring the extracellular matrix, but also play a major role in various pathophysiological conditions by virtue of their complicated expression, activation, and regulation processes. They have been widely implicated to function as major contenders in cancer progression, frequently due to their role in invasion, proliferation and metastasis. MMP inhibitors have been specifically designed to target these altered activities of MMPs, mostly by means of inhibiting their function and by diminishing their increased expression in various disease states, particularly cancer. Tetracyclines and chemically modified tetracyclines (CMTs) have been rationally designed to inhibit the activity of MMPs and thus decrease the potential risk of spread of tumor cells to distant sites by invasion and metastasis. Pre-clinical and early clinical data for one of these CMTs, COL-3 (formerly CMT-3) indicate considerable potential for this group of anticancer agents. Further testing and rational modifications of these CMT analogues might lead to new anticancer agents.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Enzyme Activation ; Enzyme Inhibitors/pharmacology ; Humans ; Matrix Metalloproteinase Inhibitors ; Matrix Metalloproteinases/physiology ; Neoplasms/pathology ; Tetracyclines/pharmacology
Chemical Substances	Antineoplastic Agents ; Enzyme Inhibitors ; Matrix Metalloproteinase Inhibitors ; Tetracyclines ; tetracycline CMT-3 ; Matrix Metalloproteinases (EC 3.4.24.-)
Language	English
Publishing date	2004-06
Publishing country	Scotland
Document type	Journal Article ; Review
ZDB-ID	1474513-6
ISSN	1532-2084 ; 1368-7646
ISSN (online)	1532-2084
ISSN	1368-7646
DOI	10.1016/j.drup.2004.04.002
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Zs.A 5099: Show issues

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Article: Determination of fraction unbound docetaxel using microequilibrium dialysis.

Acharya, Milin R / Baker, Sharyn D / Verweij, Jaap / Figg, William D / Sparreboom, Alex

Analytical biochemistry

2004 Volume 331, Issue 1, Page(s) 192–194

MeSH term(s)	Antineoplastic Agents, Phytogenic/blood ; Antineoplastic Agents, Phytogenic/pharmacokinetics ; Antineoplastic Agents, Phytogenic/therapeutic use ; Breast Neoplasms/drug therapy ; Dialysis/methods ; Female ; Humans ; Taxoids/pharmacokinetics ; Taxoids/therapeutic use
Chemical Substances	Antineoplastic Agents, Phytogenic ; Taxoids ; docetaxel (15H5577CQD)
Language	English
Publishing date	2004-08-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1110-1
ISSN	1096-0309 ; 0003-2697
ISSN (online)	1096-0309
ISSN	0003-2697
DOI	10.1016/j.ab.2004.03.045
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Zs.A 389: Show issues

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Article: Mechanisms of resistance to anticancer drugs: the role of the polymorphic ABC transporters ABCB1 and ABCG2.

Lepper, Erin R / Nooter, Kees / Verweij, Jaap / Acharya, Milin R / Figg, William D / Sparreboom, Alex

Pharmacogenomics

2005 Volume 6, Issue 2, Page(s) 115–138

Abstract: ATP-binding cassette (ABC) genes play a role in the resistance of malignant cells to anticancer agents. The ABC gene products, including ABCB1 (P-glycoprotein) and ABCG2 (breast cancer-resistance protein [BCRP], mitoxantrone-resistance protein [MXR], or ... ...

Abstract	ATP-binding cassette (ABC) genes play a role in the resistance of malignant cells to anticancer agents. The ABC gene products, including ABCB1 (P-glycoprotein) and ABCG2 (breast cancer-resistance protein [BCRP], mitoxantrone-resistance protein [MXR], or ABC transporter in placenta [ABCP]), are also known to influence oral absorption and disposition of a wide variety of drugs. As a result, the expression levels of these proteins in humans have important consequences for an individual's susceptibility to certain drug-induced side effects, interactions, and treatment efficacy. Naturally occurring variants in ABC transporter genes have been identified that might affect the function and expression of the protein. This review focuses on recent advances in the pharmacogenetics of the ABC transporters ABCB1 and ABCG2, and discusses potential implications of genetic variants for the chemotherapeutic treatment of cancer.
MeSH term(s)	ATP Binding Cassette Transporter, Sub-Family B ; ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters/genetics ; ATP-Binding Cassette Transporters/physiology ; ATP-Binding Cassette, Sub-Family B, Member 1 ; Antineoplastic Agents/pharmacokinetics ; Antineoplastic Agents/pharmacology ; Area Under Curve ; Biological Transport/physiology ; Drug Resistance, Neoplasm/genetics ; Humans ; Neoplasm Proteins/genetics ; Neoplasm Proteins/physiology ; Organic Anion Transporters/genetics ; Organic Anion Transporters/physiology ; Polymorphism, Genetic
Chemical Substances	ABCB1 protein, human ; ABCG2 protein, human ; ATP Binding Cassette Transporter, Sub-Family B ; ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette, Sub-Family B, Member 1 ; Antineoplastic Agents ; Neoplasm Proteins ; Organic Anion Transporters
Language	English
Publishing date	2005-03
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2019513-8
ISSN	1744-8042 ; 1462-2416
ISSN (online)	1744-8042
ISSN	1462-2416
DOI	10.1517/14622416.6.2.115
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Zs.A 5247: Show issues

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Article: Identification of OATP1B3 as a high-affinity hepatocellular transporter of paclitaxel.

Smith, Nicola F / Acharya, Milin R / Desai, Neil / Figg, William D / Sparreboom, Alex

Cancer biology & therapy

2005 Volume 4, Issue 8, Page(s) 815–818

Abstract: Interindividual variability in paclitaxel and docetaxel pharmacokinetics, toxicity and response is extensive, and largely unexplained. We hypothesized that this is due to affinity of taxanes for an uptake transporter that indirectly regulates elimination ...

Abstract	Interindividual variability in paclitaxel and docetaxel pharmacokinetics, toxicity and response is extensive, and largely unexplained. We hypothesized that this is due to affinity of taxanes for an uptake transporter that indirectly regulates elimination pathways. Here, we studied accumulation of [3H]docetaxel and [3H]paclitaxel in Xenopus laevis oocytes injected with cRNA of the liver-specific organic anion transporting polypeptide (OATP) family members OATP1B1 (OATP2) or OATP1B3 (OATP8). Taxane transport by OATP1B1 expressing oocytes was not significantly different from that by water-injected controls, whereas uptake by OATP1B3 was 2.2-fold higher for docetaxel (p = 0.0007) and 3.3-fold higher for paclitaxel (p < 0.0001). OATP1B3-mediated paclitaxel transport was saturable (Michaelis-Menten constant, 6.79 microM), time-dependent, and highly sensitive to chemical inhibition. Paclitaxel uptake was not inhibited by ketoconazole or tariquidar. However, uptake was inhibited by the formulation excipient Cremophor (74.4% inhibition, p < 0.0001), cyclosporin A (25.2%, p = 0.005), glycyrrhizic acid (24.6%, p = 0.012), and hyperforin (28.4%, p = 0.003). Consistent with this finding, Cremophor was found to significantly affect the hepatic uptake of paclitaxel in mice. These data suggest that OATP1B3 is a key regulator of hepatic uptake, and may therefore play a role in the variable response to treatment with taxanes.
MeSH term(s)	Animals ; Antineoplastic Agents, Phytogenic/metabolism ; Female ; Hepatocytes/drug effects ; Hepatocytes/metabolism ; Humans ; Ketoconazole/pharmacology ; Liver/cytology ; Liver/drug effects ; Liver/metabolism ; Liver-Specific Organic Anion Transporter 1 ; Mice ; Mice, Inbred Strains ; Oocytes/metabolism ; Organic Anion Transporters/genetics ; Organic Anion Transporters/physiology ; Organic Anion Transporters, Sodium-Independent/antagonists & inhibitors ; Organic Anion Transporters, Sodium-Independent/genetics ; Organic Anion Transporters, Sodium-Independent/physiology ; Paclitaxel/metabolism ; Quinolines/pharmacology ; Solute Carrier Organic Anion Transporter Family Member 1B3 ; Xenopus laevis
Chemical Substances	Antineoplastic Agents, Phytogenic ; Liver-Specific Organic Anion Transporter 1 ; Organic Anion Transporters ; Organic Anion Transporters, Sodium-Independent ; Quinolines ; SLCO1B1 protein, human ; SLCO1B3 protein, human ; Solute Carrier Organic Anion Transporter Family Member 1B3 ; tariquidar (J58862DTVD) ; Paclitaxel (P88XT4IS4D) ; Ketoconazole (R9400W927I)
Language	English
Publishing date	2005-10-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2146305-0
ISSN	1538-4047
ISSN	1538-4047
DOI	10.4161/cbt.4.8.1867
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Zs.A 5887: Show issues

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Article: Interspecies differences in plasma protein binding of MS-275, a novel histone deacetylase inhibitor.

Acharya, Milin R / Sparreboom, Alex / Sausville, Edward A / Conley, Barbara A / Doroshow, James H / Venitz, Jurgen / Figg, William D

Cancer chemotherapy and pharmacology

2006 Volume 57, Issue 3, Page(s) 275–281

Abstract: MS-275 (MS-27-275; 3-pyridylmethyl-N-[4-[(2-aminophenyl)-carbamoyl]-benzyl-carbamate) is a histone deacetylase inhibitor under clinical development as an anticancer agent. Here, we examined the role of protein binding as a possible determinant of the ... ...

Abstract	MS-275 (MS-27-275; 3-pyridylmethyl-N-[4-[(2-aminophenyl)-carbamoyl]-benzyl-carbamate) is a histone deacetylase inhibitor under clinical development as an anticancer agent. Here, we examined the role of protein binding as a possible determinant of the pharmacokinetic behavior of MS-275. The distribution of MS-275 in plasma was studied in vitro using equilibrium dialysis and ex vivo in five cancer patients receiving the drug orally at a dose of 10 mg/m(2). The dialysis method uses a tracer amount of [G-(3)H]MS-275 on a 96-well microdialysis plate with a 5-kDa cut-off membrane, and requires 250 microl sample. The time to equilibrium was established to be within 5 h, and the mean unbound fraction of MS-275 (f (u)) over a presumed therapeutic concentration range in healthy volunteer human plasma was 0.188 +/- 0.0075 as compared to 0.168 +/- 0.0144 in cancer patients. The binding was concentration-independent, indicating a low affinity, possibly non-specific and non-saturable process. MS-275 was found to bind in decreasing order to plasma > alpha(1)-acid glycoprotein > albumin. Among 19 tested drugs, a slightly increased f (u) was observed in the presence of only ibuprofen (f (u), 0.236 +/- 0.001) and metoclopramide (f (u), 0.270 +/- 0.042), suggesting weakly competitive displacement from protein-binding sites (P < 0.01). Compared to humans, f (u) was significantly higher in plasma from mouse (0.376), rat (0.393), rabbit (0.355), dog (0.436), and pig (0.439) (P < 0.01), which may explain, in part, the species-dependent pharmacokinetic profile of MS-275 observed previously.
MeSH term(s)	Animals ; Area Under Curve ; Benzamides/blood ; Benzamides/metabolism ; Benzamides/pharmacokinetics ; Binding, Competitive/drug effects ; Blood Proteins/metabolism ; Dogs ; Glycoproteins/metabolism ; Half-Life ; Histone Deacetylase Inhibitors ; Humans ; Ibuprofen/pharmacology ; Metoclopramide/pharmacology ; Mice ; Neoplasms/blood ; Neoplasms/metabolism ; Orosomucoid ; Protein Binding/drug effects ; Pyridines/blood ; Pyridines/metabolism ; Pyridines/pharmacokinetics ; Rabbits ; Rats ; Serum Albumin/metabolism ; Species Specificity ; Swine ; Time Factors
Chemical Substances	Benzamides ; Blood Proteins ; Glycoproteins ; Histone Deacetylase Inhibitors ; Orm1 protein, rat ; Orosomucoid ; Pyridines ; Serum Albumin ; entinostat (1ZNY4FKK9H) ; Metoclopramide (L4YEB44I46) ; Ibuprofen (WK2XYI10QM)
Language	English
Publishing date	2006-02
Publishing country	Germany
Document type	Comparative Study ; Journal Article
ZDB-ID	6820-2
ISSN	1432-0843 ; 0344-5704 ; 0943-9404
ISSN (online)	1432-0843
ISSN	0344-5704 ; 0943-9404
DOI	10.1007/s00280-005-0058-8
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Zs.A 1420: Show issues

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Article: Factors affecting the pharmacokinetic profile of MS-275, a novel histone deacetylase inhibitor, in patients with cancer.

Acharya, Milin R / Karp, Judith E / Sausville, Edward A / Hwang, Kyunghwa / Ryan, Qin / Gojo, Ivana / Venitz, Jurgen / Figg, William D / Sparreboom, Alex

Investigational new drugs

2006 Volume 24, Issue 5, Page(s) 367–375

Abstract: ... ideal body weight (p = 0.02, |r| = 0.29), none of the studied measures (BSA, lean-body mass, ideal body weight ... body-mass index, height, weight, age, and sex) was a significant covariate (p > 0.13; |r| < 0.11) for oral ...

Abstract	Aims: To evaluate elimination pathways of the histone deacetylase inhibitor MS-275 in vitro and screen for relationships between demographic factors that may affect its pharmacokinetics in vivo. Patients and methods: Substrate specificity of MS-275 for the liver-specific organic anion transporting polypeptides (OATPs) was assessed using Xenopus laevis oocytes, and in vitro metabolism was evaluated using human liver microsomes. In vivo pharmacokinetic data were obtained from 64 adult patients (36 male/28 female; median age, 57 years) receiving MS-275 orally (dose range, 2 to 12 mg/m2). Results: Accumulation of [G-3H]MS-275 by oocytes expressing OATP1B1 or OATP1B3 was not significantly different from water-injected controls (p = 0.82). Furthermore, no metabolites could be detected after incubation of MS-275 in human liver microsomes, suggesting that hepatic metabolism is a minor pathway of elimination. The mean (+/- SD) apparent oral clearance of MS-275 was 38.5 +/- 18.7 L/h, with a coefficient of variation (%CV) of 48.7%. When clearance was adjusted for body-surface area (BSA), the inter-individual variability was similar (%CV = 50.1%). In addition, in a linear-regression analysis, except for adjusted ideal body weight (p = 0.02, \|r\| = 0.29), none of the studied measures (BSA, lean-body mass, ideal body weight, body-mass index, height, weight, age, and sex) was a significant covariate (p > 0.13; \|r\| < 0.11) for oral clearance. Conclusions: The current analysis has eliminated a number of candidate covariates from further consideration as important determinants of MS-275 absorption and disposition. Furthermore, MS-275 can be added to the list of cancer drugs where BSA-based dosing is not more accurate than fixed dosing.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Animals ; Antineoplastic Agents/blood ; Antineoplastic Agents/pharmacokinetics ; Antineoplastic Agents/therapeutic use ; Benzamides/blood ; Benzamides/pharmacokinetics ; Benzamides/therapeutic use ; Body Mass Index ; Body Surface Area ; Body Weight ; Cells, Cultured ; Enzyme Inhibitors/blood ; Enzyme Inhibitors/pharmacokinetics ; Enzyme Inhibitors/therapeutic use ; Female ; Histone Deacetylase Inhibitors ; Humans ; Male ; Microsomes, Liver/metabolism ; Middle Aged ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Oocytes/metabolism ; Organic Anion Transporters/metabolism ; Pyridines/blood ; Pyridines/pharmacokinetics ; Pyridines/therapeutic use ; Xenopus laevis
Chemical Substances	Antineoplastic Agents ; Benzamides ; Enzyme Inhibitors ; Histone Deacetylase Inhibitors ; Organic Anion Transporters ; Pyridines ; entinostat (1ZNY4FKK9H)
Language	English
Publishing date	2006-09
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article
ZDB-ID	604895-x
ISSN	1573-0646 ; 0167-6997
ISSN (online)	1573-0646
ISSN	0167-6997
DOI	10.1007/s10637-005-5707-6
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Zs.A 1823: Show issues

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Article: Determination of MS-275, a novel histone deacetylase inhibitor, in human plasma by liquid chromatography-electrospray mass spectrometry.

Hwang, Kyunghwa / Acharya, Milin R / Sausville, Edward A / Zhai, Suoping / Woo, Eunhee W / Venitz, Jürgen / Figg, William D / Sparreboom, Alex

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

2004 Volume 804, Issue 2, Page(s) 289–294

Abstract: A rapid method was developed for the quantitative determination of the novel histone deacetylase inhibitor, MS-275, in human plasma. Calibration curves were constructed in the range of 1-100 ng/ml, and were analyzed using a weight factor proportional to ... ...

Abstract	A rapid method was developed for the quantitative determination of the novel histone deacetylase inhibitor, MS-275, in human plasma. Calibration curves were constructed in the range of 1-100 ng/ml, and were analyzed using a weight factor proportional to the nominal concentration. Sample pretreatment involved a one-step protein precipitation with acetonitrile of 0.1 ml samples. The analysis was performed on a column (75 mm x 4.6 mm i.d.) packed with 3.5 microm Phenyl-SB material, using methanol-10mM ammonium formate (55:45 (v/v)) as the mobile phase. The column effluent was monitored by mass spectrometry with positive electrospray ionization. The values for precision and accuracy were always < or =5.58 and <11.4% relative error, respectively. The method was successfully applied to examine the pharmacokinetics of MS-275 in a cancer patient.
MeSH term(s)	Administration, Oral ; Benzamides/administration & dosage ; Benzamides/blood ; Benzamides/pharmacokinetics ; Chromatography, Liquid/methods ; Enzyme Inhibitors/administration & dosage ; Enzyme Inhibitors/blood ; Enzyme Inhibitors/pharmacokinetics ; Histone Deacetylase Inhibitors ; Humans ; Pyridines/administration & dosage ; Pyridines/blood ; Pyridines/pharmacokinetics ; Reproducibility of Results ; Spectrometry, Mass, Electrospray Ionization/methods
Chemical Substances	Benzamides ; Enzyme Inhibitors ; Histone Deacetylase Inhibitors ; Pyridines ; entinostat (1ZNY4FKK9H)
Language	English
Publishing date	2004-05-25
Publishing country	Netherlands
Document type	Journal Article
ISSN	1570-0232
ISSN	1570-0232
DOI	10.1016/j.jchromb.2004.01.023
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