Predictive model for plasma concentration-versus-time profiles of investigational anticancer drugs in patientsi

Lisa E. Davis, David S Alberts, Patricia M. Plezia, Denise Roe, Daniel P. Griswold

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

We report a model that provides a strong correlation between mouse toxicity data [mouse lethal dose 10% (LD10)] and human plasma concentration-versus-time (CXT) data for 22 commonly used anticancer agents. Mouse toxicity data (LD10) from two dosing schedules, daily times one and daily times seven, were evaluated for the two mouse strains BDF/1 and Swiss. Data from BDF/1 mice were selected for analysis because they were more abundant. Strong correlations were found between LD10 and human plasma CXT data for both daily times one and daily times seven dosing schedules-In (CXT) = -1.6504 + [0.8408 × In (LD10)], r = .84, P < .0001, and In (CXT) = -0.0754 + [0.8954 × In (LD10)], r = .90, P < .0001, respectively. These correlations may serve as useful models to predict the maximally tolerated dose of an investigational anticancer agent prior to entry into clinical trials and to assist in the selection of clinically relevant in vitro CXTs for new-agent screening against human tumors.

Original languageEnglish (US)
Pages (from-to)815-819
Number of pages5
JournalJournal of the National Cancer Institute
Volume80
Issue number11
DOIs
StatePublished - Aug 3 1988

Fingerprint

Investigational Drugs
Predictive Model
Plasma (human)
Dose
Drugs
Plasma
Mouse
Plasmas
Toxicity
Antineoplastic Agents
Appointments and Schedules
Tumors
Screening
Schedule
Maximum Tolerated Dose
Clinical Trials
Profile
Tumor
Predict
Neoplasms

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Radiology Nuclear Medicine and imaging
  • Oncology
  • Cancer Research

Cite this

Predictive model for plasma concentration-versus-time profiles of investigational anticancer drugs in patientsi. / Davis, Lisa E.; Alberts, David S; Plezia, Patricia M.; Roe, Denise; Griswold, Daniel P.

In: Journal of the National Cancer Institute, Vol. 80, No. 11, 03.08.1988, p. 815-819.

Research output: Contribution to journalArticle

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