Open Label Study for the Functional Characterization of Drug Metabolism and Transport
Condition: Genotype-related Drug Metabolism
Study type: Interventional
Phase: Phase 1

Summary: 
      Aim of this study is to comprehensively assess in healthy volunteers the metabolic processes
      and factors that define drug response. Sources of variability are to be investigated and
      factors that can alter the hepatic metabolism and the pharmacokinetics of drugs shall be
      quantified.

      Determination of variability is important when the pharmacokinetics of new drugs is being
      investigated and when the concept of individualized medicine is to be further developed. It
      is important to identify and differentiate between pharmaceutical, physiological (e.g. liver
      blood flow, renal function), environmental (e.g. foods and lifestyle), and genetic sources of
      inter-individual variability. For instance, inaccurate or false conclusions may be drawn from
      a single pharmacokinetic study, if the investigated medicine is metabolized by an enzyme with
      large inter-individual variability. Knowing the causes of variability and of the quantitative
      contribution of various processes might help to improve the oral formulations of drugs, might
      help selecting the right preclinical tests and selection criteria during clinical
      development, provide the basis to understand the influence of disease and to optimize
      established drug treatments in order to make future drug treatment safer and more efficient.

      This study is designed as an add-on to the study "TWINS: Open Label Repeated Dose Study for
      the Evaluation of Heritability of and Genetic Influences on Drug Pharmacokinetics" (Eudra-CT:
      2008-006223-31). Twins are not a random sample of the population, and they differ in their
      developmental environment. In this sense they are not representative for the population Thus,
      the results of TWINS cannot be automatically generalized but instead require validation in a
      representative population sample. While both studies assess pharmacologic factors important
      for drug response, TWINS contributes in particular data on the heritability of these
      processes.
    


Intervention name(s): Codeine; Midazolam; pravastatin; Talinolol; torsemide
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): A single oral low dose of codeine 5 mg and midazolam 1 mg administered as drop, pravastatin 5 mg, talinolol 2.5 mg, and torsemide 0.25 mg provided in capsules will be given together at the same time point (cocktail).; A single oral low dose of codeine 5 mg and midazolam 1 mg administered as drop, pravastatin 5 mg, talinolol 2.5 mg, and torsemide 0.25 mg provided in capsules will be given together at the same time point (cocktail).; A single oral low dose of codeine 5 mg and midazolam 1 mg administered as drop, pravastatin 5 mg, talinolol 2.5 mg, and torsemide 0.25 mg provided in capsules will be given together at the same time point (cocktail).; A single oral low dose of codeine 5 mg and midazolam 1 mg administered as drop, pravastatin 5 mg, talinolol 2.5 mg, and torsemide 0.25 mg provided in capsules will be given together at the same time point (cocktail).; A single oral low dose of codeine 5 mg and midazolam 1 mg administered as drop, pravastatin 5 mg, talinolol 2.5 mg, and torsemide 0.25 mg provided in capsules will be given together at the same time point (cocktail).
Intervention MeSH terms: Talinolol; Torsemide; Midazolam; Codeine; Pravastatin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: pharmacokinetic/genetic; Cyp450 polymorphisms; Noninvasive functional characterization of liver heart and kidneys using MRI