Linear drugs

From a pharmacological viewpoint, the compounds of interest that undergo metabolic cyclization include ring-opened prodrugs of cyclic drugs [82], or linear drugs that yield a cyclic (and often inactive) metabolite. In the subsections below, we first examine cyclizations, which eliminate a halide or a relatively large molecule, and then proceed to discuss reactions of dehydration. 

In silico modeling of non-linear drug absorption for the P-gp substrate talinolol and of consequences for the resulting pharmacodynamic effect. Pharmaceutical Research, 23, 1712-1720. 

Pillay V, Danckwerts MP, Fassihi R. A crosslinked calcium-alginate-pectinate-cellulose acetophthalate gelisphere system for linear drug release. Drug Delivery 2002 9(2) 77-86. 

Perkins EJ, Abraham T (2007) Pharmacokinetics, metabolism, and excretion of the intestinal peptide transporter 1 (SLC15Al)-targeted prodrug (IS, 2S, 5R, 6S)-2-[(2 S)-(2-amino)propionyl]aminobicyclo[3.1.0.]hexen-2, 6-di carboxylic acid (LY544344) in rats and dogs assessment of first-pass bioactivation and dose linearity. Drug Metab Dispos 35 1903-1909... 

When plasma concentration, unbound concentration, the amount of drug and metabolite excreted and so forth all increase in proportion to dose, then the superposition principle applies. This means that concentration over time of a multidose treatment schedule can be calculated as the sum of the concentrations which would be observed from the individual doses were they given alone. For such drugs, the pharmacokinetics are said to be dose-independent or linear. Drugs which do not exhibit dose-proportionality can be difficult to manage. (A notorious example is alcohol.)... 

Linear drug disposition is dehned as a linear relationship (L) between the input, 7, of drug into the systemic circulation and the resulting measured concentration, C, of drug in the systemic circulation ... 

In a structured modeling context, linear drug disposition is commonly thought of as a disposition governed by first-order processes. Contrary to this, the LSA approach defines linear disposition independently of the structure of the disposition processes (distribution and elimination). Linear disposition is simply a linear relationship (L) between input (7) and the measured systemic drug concentration, C. A so-called nonlinear absorption is sometimes observed in oral administrations when... 

The LSA linear drug disposition definition does not impose any restrictions on the mathematical form of the drug input response. This is in contrast to linear compartmental models. For example, a two-compartment model implies a biexponential response to an IV bolus injection ... 

Consider, for example, a linear drug with a polyexponential UIR as given above. Let the input be first order and discontinued at time = T, so that... 

Example 16.3 Biexponential Linear Drug Disposition. Consider a drug with a linear disposition and a biexponential concentration response resulting from an TV bolus injection. 

S. Borodkin, F.E. Tucker, Linear drug release from... 

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