Document 0527
 DOCN  M9550527
 TI    A direct, general approach based on isobolograms for assessing the joint
       action of drugs in pre-clinical experiments.
 DT    9505
 AU    Machado SG; Robinson GA; Division of Biometrics, Food and Drug
       Administration, Rockville,; MD 20857.
 SO    Stat Med. 1994 Nov 30;13(22):2289-309. Unique Identifier : AIDSLINE
       MED/95158741
 AB    Pharmacologists and other biologists frequently use methods based on the
       interpretation of isobolograms to quantify the extent of synergy or
       antagonism between drugs used in combination in pre-clinical studies.
       Most methods have been unsatisfactory from a statistical viewpoint, many
       because they have relied solely on visual evaluation, others because the
       methods have not taken into account the variability of the measurements.
       We describe a direct approach for quantifying the joint potency of two
       drugs, a central feature being the use of simple isobole models that
       lead directly to response surface models for the expected experimental
       outcomes. The approach is general in the sense that one can use it for
       discrete or continuous responses, different underlying probability
       distributions, linear or non-linear dose-response functions of the drugs
       used singly, and a variety of experimental designs. Our approach extends
       the suggestions made by Hewlett for measuring the joint potency of
       drugs, and is similar in spirit to the approaches proposed by Greco et
       al. and Weinstein et al. We describe the analysis of data from an in
       vitro experiment conducted to evaluate the efficacy of the antiviral
       drugs AZT and ddI used in combination.
 DE    Comparative Study  Didanosine/PHARMACOLOGY  Dose-Response Relationship,
       Drug  Drug Antagonism  *Drug Combinations  *Drug Interactions  *Drug
       Screening  Drug Synergism  Human  HIV-1/DRUG EFFECTS  *Models,
       Theoretical  Zidovudine/PHARMACOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).