Based on disposition decomposition analysis (DDA), equations for the mean residence times (MRT) in the body are derived for a drug and its interconversion metabolite that undergo linear tissue distribution and linear or non-linear elimination from the central compartment after non-instantaneous admi
An algorithm and computer program for calculating the mean transit time and distribution rate parameters of generated metabolites undergoing linear tissue distribution and linear or non-linear central elimination
โ Scribed by Haiyung Cheng; Chi Yu; William J. Jusko
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- English
- Weight
- 752 KB
- Volume
- 15
- Category
- Article
- ISSN
- 0142-2782
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โฆ Synopsis
A method is described for calculating the mean transit time and distribution rate parameters of a generated primary metabolite undergoing linear distribution and linear or non-linear central elimination, and of catenary metabolites with any precursor order. It is also applicable to a drug and its interconversion metabolite and does not require separate administration of the metabolite. The method allows steady-state volume of distribution and distribution clearance of a metabolite to be calculated, provided that the central volume of distribution of the metabolite is known. An algorithm and computer program to implement the proposed method are presented. The calculations require the plasma concentration versus time curves of the metabolite and its precursor. The method is applied to both published and simulated data. KEY WORDS Mean transit time Catenary metabolites Distribution clearance Steady-state volume of distribution Distribution rate parameters Interconversion metabolites state volume of distribution ( Vss) are dose independent in pharmacokinetic systems with linear tissue distribution and non-linear central eliminati~n.~ *To whom correspondence should be addressed.
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