Pharmacokinetics of the hypoxic cell cytotoxic agent tirapazamine and its major bioreductive metabolites in mice and humans: retrospective analysis of a pharmacokinetically guided dose-escalation strategy in a phase I trial

Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey, and man.

1966 • 1,363 citations

Fundamentals of Clinical Pharmacokinetics

1975 • 1,035 citations

SR 4233 (Tirapazamine): a new anticancer drug exploiting hypoxia in solid tumours

1993 • 354 citations

Direct measurement of pO2 distribution and bioreductive enzymes in human malignant brain tumors

1994 • 301 citations

Potential roles for preclinical pharmacology in phase I clinical trials.

1986 • 213 citations

Potentiation by the hypoxic cytotoxin SR 4233 of cell killing produced by fractionated irradiation of mouse tumors.

1990 • 184 citations

Tumor-specific, schedule-dependent interaction between tirapazamine (SR 4233) and cisplatin.

1993 • 144 citations

Normalization in the fitting of data by iterative methods. Application to tracer kinetics and enzyme kinetics

1973 • 100 citations

Repair of DNA and chromosome breaks in cells exposed to SR 4233 under hypoxia or to ionizing radiation.

1992 • 88 citations

The role of cytochrome P450 and cytochrome P450 reductase in the reductive bioactivation of the novel benzotriazine di-N-oxide hypoxic cytotoxin 3-amino-l,2,4-benzotriazine-l ,4-dioxide (SR 4233, WIN 59075) by mouse liver

1992 • 78 citations

Pharmacology and Clinical Toxicity of 4'-Iodo-4'-deoxydoxorubicin: An Example of Successful Application of Pharmacokinetics to Dose Escalation in Phase I Trials

1990 • 73 citations

Enzymology of the reductive bioactivation of SR 4233

1990 • 69 citations

Reduction of 3-amino-l,2,4-benzotriazine-l,4-di-N-oxide (tirapazamine, WIN 59075, SR 4233) to a DNA-damaging species: a direct role for NADPH: cytochrome P450 oxidoreductase

1994 • 64 citations

The impact of pharmacokinetically guided dose escalation strategies in phase I clinical trials: Critical evaluation and recommendations for future studies

1992 • 46 citations

Pharmacokinetics and bioreductive metabolism of the novel benzotriazine di-N-oxide hypoxic cell cytotoxin tirapazamine (WIN 59075; SR 4233; NSC 130181) in mice.

1993 • 33 citations

Initial characterization of the major mouse cytochrome p450 enzymes involved in the reductive metabolism of the hypoxic cytotoxin 3-Amino-1,2,4-Benzotriazine-1,4-di-N-Oxide (Tirapazamine, SR 4233, Win 59075)

1993 • 30 citations

Application of Pharmacokinetically Guided Dose Escalation With Respect to Cell Cycle Phase Specificity

1994 • 25 citations

Toxicology of daily administration to mice of the radiation potentiator SR 4233 (WIN 59075)

1993 • 13 citations

New approaches in preclinical and clinical pharmacokinetics.

1993 • 11 citations

Development and validation of a sensitive solid-phase-extraction and high-performance liquid chromatography assay for the bioreductive agent tirapazamine and its major metabolites in mouse and human plasma for pharmacokinetically guided dose escalation

1995 • 7 citations