Clinical pharmacology of UCN-01: Initial observations and comparison to preclinical models

Edward A. Sausville; Richard D. Lush; Donna Headlee; Adaline C. Smith; William D. Figg; Susan G. Arbuck; Adrian M. Senderowicz; Eiichi Fuse; Hiromi Tanii; Takashi Kuwabara; Satoshi Kobayashi

doi:10.1007/s002800051080

Clinical pharmacology of UCN-01: Initial observations and comparison to preclinical models

Edward A. Sausville^*, Richard D. Lush, Donna Headlee, Adaline C. Smith, William D. Figg, Susan G. Arbuck, Adrian M. Senderowicz, Eiichi Fuse, Hiromi Tanii, Takashi Kuwabara, Satoshi Kobayashi

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

83 Scopus citations

Abstract

UCN-01 (7-hydroxystaurosporine; NSC 638850) is a protein kinase antagonist selected for clinical trial based in part on evidence of efficacy in a preclinical renal carcinoma xenograft model. Schedule studies and in vitro studies suggested that a 72-h continuous infusion would be appropriate. In rats and dogs, maximum tolerated doses produced peak plasma concentrations of approximately 0.2-0.3 μM. However, concentrations 10-fold greater are well tolerated in humans, and the compound has a markedly prolonged T( 1/4 ). Specific binding to human α₁-acidic glycoprotein has been demonstrated. These findings reinforce the need to consider actual clinical pharmacology data in 'real time' with phase I studies.

Original language	English
Pages (from-to)	S54-S59
Journal	Cancer Chemotherapy and Pharmacology, Supplement
Volume	42
DOIs	https://doi.org/10.1007/s002800051080
State	Published - Aug 1998
Externally published	Yes

Keywords

Protein kinase antagonist
Staurosporine, 7-hydroxy
α-Acidic glycoprotein

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10.1007/s002800051080

Cite this

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abstract = "UCN-01 (7-hydroxystaurosporine; NSC 638850) is a protein kinase antagonist selected for clinical trial based in part on evidence of efficacy in a preclinical renal carcinoma xenograft model. Schedule studies and in vitro studies suggested that a 72-h continuous infusion would be appropriate. In rats and dogs, maximum tolerated doses produced peak plasma concentrations of approximately 0.2-0.3 μM. However, concentrations 10-fold greater are well tolerated in humans, and the compound has a markedly prolonged T( 1/4 ). Specific binding to human α1-acidic glycoprotein has been demonstrated. These findings reinforce the need to consider actual clinical pharmacology data in 'real time' with phase I studies.",

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year = "1998",

month = aug,

doi = "10.1007/s002800051080",

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journal = "Cancer Chemotherapy and Pharmacology, Supplement",

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T2 - Initial observations and comparison to preclinical models

AU - Sausville, Edward A.

AU - Lush, Richard D.

AU - Headlee, Donna

AU - Smith, Adaline C.

AU - Figg, William D.

AU - Arbuck, Susan G.

AU - Senderowicz, Adrian M.

AU - Fuse, Eiichi

AU - Tanii, Hiromi

AU - Kuwabara, Takashi

AU - Kobayashi, Satoshi

PY - 1998/8

Y1 - 1998/8

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AB - UCN-01 (7-hydroxystaurosporine; NSC 638850) is a protein kinase antagonist selected for clinical trial based in part on evidence of efficacy in a preclinical renal carcinoma xenograft model. Schedule studies and in vitro studies suggested that a 72-h continuous infusion would be appropriate. In rats and dogs, maximum tolerated doses produced peak plasma concentrations of approximately 0.2-0.3 μM. However, concentrations 10-fold greater are well tolerated in humans, and the compound has a markedly prolonged T( 1/4 ). Specific binding to human α1-acidic glycoprotein has been demonstrated. These findings reinforce the need to consider actual clinical pharmacology data in 'real time' with phase I studies.

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KW - α-Acidic glycoprotein

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ER -

Clinical pharmacology of UCN-01: Initial observations and comparison to preclinical models

Abstract

Keywords

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