Pharmacogenetics in the Field of Heme Metabolism: Drug Sensitivity in Hereditary Hepatic Porphyria

  • J. Douglas Maxwell
  • Urs A. Meyer
Part of the Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology book series (HEP, volume 44)


Sir Archibald Garrod (1902), who pioneered the study of inborn errors of metabolism, was the first to suggest that unusual reactions to drugs might be caused by genetically determined aberrations in metabolic pathways. This far-sighted observation was neglected for many years. However, with the recognition in the 1950’s that several “idiosyncratic” drug reactions, such as primaquine-induced hemolytic anemia and suxamethonium-induced prolonged apnoea, could be explained on the basis of genetically determined enzyme deficiencies, pharmacogenetics was established. Initially, the term referred only to hereditary disorders involving adverse reactions to drugs that were uncovered by administration of the particular agents. This definition seemed too restrictive, as it excluded from consideration genetically determined differences in drug metabolism or disposition (pharmacokinetics) and drug response (pharmacodynamics) between healthy non-medicated subjects (Vesell, 1975). When it became apparent that the interplay between genetics and pharmacology influenced the action of many drugs, the scope of pharmacogenetics was extended to include all studies at the interface of these two sciences. Pharmacogenetics now incorporates all clinically important hereditary variations in drug metabolism and response.


Acute Attack Heme Biosynthesis Porphyria Cutanea Tarda Heme Synthesis Intermittent Acute Porphyria 
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© Springer-Verlag Berlin Heidelberg 1978

Authors and Affiliations

  • J. Douglas Maxwell
  • Urs A. Meyer

There are no affiliations available

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