An identifiability analysis of a parent-metabolite pharmacokinetic model for ivabradine.

The paper considers the structural identifiability of a parent–metabolite pharmacokinetic model for ivabradine and one of its metabolites. The model, which is linear, is considered initially for intravenous administration of ivabradine, and then for a combined intravenous and oral administration. In both cases, the model is shown to be unidentifiable. Simplification of the model (for both forms of administration) to that proposed by Duffull et al. (1) results in a globally structurally identifiable model. The analysis could be applied to the modeling of any drug undergoing first-pass metabolism, with plasma concentrations available from drug and metabolite.

Identifiability and definiteness in Chinese

This article explores how the pragmatic notion of identfiability is encoded in Chinese. It presents a detailed analysis of the distinctive linguistic devices, including lexical, morphological, and position in sentence, which are employed in Chinese to indicate the interpretation of referents in respect of identifiability. Of the major determiners in Chinese, demonstratives are developing uses of a definite article, and yi 'one' + classier has developed uses of an indefinite article, although morphologically and in some cases also functionally they have not yet been fully grammaticalized. What makes Chinese further different from languages like English is the interpretation in this regard of what are called indeterminate lexical encodings, which include bare NPs and cardinality expressions. They by themselves are neutral in respect of the interpretation of identifiability. For indeterminate expressions, there is a strong but seldom absolute correlation between the interpretation of identiability or nonidentfiability and their occurrence in different positions in a sentence. Unlike the cases with several other languages without articles like Czech, Hindi, and Indonesian, the features of definiteness and indefiniteness cannot be obligatorily and uniquely specified for nominal expressions in Chinese. The findings in this article lead to the conclusion that definiteness as a grammatical category defined in the narrow sense has not been fully developed in Chinese.