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By Roger P. Maickel (auth.), Eric Reid, Ian D. Wilson (eds.)

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48, 123-131. J. M. (1976) 1. Chroma tog. 121, 96-99. Ander, P. J. (1965) Principles of Chemistry, Collier-Macmillan, London; see pp. 747-750. 45 #NC(A) NOTES and COMMENTS relating to Sample handling and usfulness of isotopes Comments related to particular contributions #A-1, #A-3 & #A-4, p. 61 #NC(A)-2, p. 62 (See p. 375 for points relevant to #A-2) 47 #NC(A)-l A Note on APPROACHES FOR DETERMINING ETHYLENEDIAMINE AND ITS METABOLITES: USE OF [14C]_ AND [DtJ-ETHYLENEDIAMINE John Caldwell and Ian A.

The methodology was developed earlier in animal studies or applied to enzyme preparations, but this is not exemplified. The co-administration approach can give dramatic insights into the fate of drugs (or other compounds) in living systems, and important guidance for the long-term treatment of patients, not obtainable by other means. Co-administration excludes biological variations with time, giving fewer but considerably more meaningful observations. We consider in turn the choice of labelled molecule, the question of 'isotope effects', and limits of detection with 'real' samples.

100 ~ .... ;:1 . 3() r······· .. , [A-3 ~ " . •••••• : ••••••• : •••• - ~ > 10 "'E VI ;:;:'" o b o 6 o ,~ o Time. h would have a lower maximum and decline more steeply • The half-life for carbamazepine is -28 h after a single dose, -12 h under monotherapy and only -8 h under combined anti epileptic therapy [13]. This is an example which is representative for several antiepileptic drugs. Pharmacokinetic parameters from single-dose studies in healthy volunteers are essential, but are often unrepresentative of patients under long-term treatment.

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