Abstract
Current interest in drug targeting has inspired theoretical considerations of its potential and problems. Previously, drug targeting has been considered in terms of more or less elaborate compartmental models. The present paper shows how an equivalent analysis of the potential advantage of drug targeting may be derived with the minimum reliance on a specific model. A linear recirculation model is used to describe the drug concentration profile at some target site and in the rest of the body. Equations for theAUCs of drug and of a drug-carrier conjugate can then be derived. TheseAUCs are used to define a drug targeting index (DTI), a measure of drug targeting selectivity previously derived from a specific model. It is shown that theDTI can be defined solely in terms of extraction ratios for elimination of free drug, when release of drug is confined to the target site. The expression forDTI is shown to be equivalent to that previously derived from several more model-dependent approaches.
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Abbreviations
- R:
-
The target compartment
- S:
-
The rest of the body outside of the target compartment
- Q :
-
Flow or transport clearance describing the movement of species between the compartments
- E R(D) :
-
That fraction of drug eliminated during one passage through R
- E S(D) :
-
That fraction of drug eliminated during one passage through S
- E S(DC) :
-
That fraction of drug carrier eliminated during one passage through S
- E S(DC→D) :
-
That fraction of drug carrier which releases drug during one passage through S
- E R(DC→D) :
-
That fraction of drug carrier which releases drug during one passage through R
- H D(t):
-
Rate of input of drug into S
- H DC(t):
-
Rate of input of drug carrier into S
- D s(t):
-
Drug concentration in S following input of drug
- D R(t):
-
Drug concentration in R following input of drug
- DC s(t):
-
Drug carrier concentration in S
- DC R(t):
-
Drug carrier concentration in R
- DX x(t):
-
Drug concentration in S following input of drug carrier
- DX R(t):
-
Drug concentration in R following input of drug carrier
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Boddy, A.V., Aarons, L.J. Application of a linear recirculation model to drug targeting. Journal of Pharmacokinetics and Biopharmaceutics 19, 355–362 (1991). https://doi.org/10.1007/BF03036256
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DOI: https://doi.org/10.1007/BF03036256