Elimination half life selected drugs

The formation of active metabolites has complicated studies on the pharmacokinetics of the benzodiazepines in humans because the elimination half-life of the parent drug may have little relationship to the time course of pharmacologic effects. Those benzodiazepines for which the parent drug or active metabolites have long half-lives are more likely to cause cumulative effects with multiple doses. Cumulative and residual effects such as excessive drowsiness appear to be less of a problem with such drugs as estazolam, oxazepam, and lorazepam, which have shorter half-lives and are metabolized directly to inactive glucuronides. Some pharmacokinetic properties of selected benzodiazepines are listed in Table 22-1. 

Now take an essentially sound experimental design. We want to determine the average elimination half-life of a new anti-diabetic drug in type II diabetics aged 50-75, within Western Europe. We recruit several hospitals scattered throughout Western Europe and they draw up a census of all the appropriately aged, type II diabetics under their care. From these lists we then randomly select potential subjects. 

Influence of Volume of Distribution (V) on Elimination Half-Life (ti/ ) for Selected Drugs with Similar Clearance Values (Cl) (Data from Appendix Table A-II in Hardman et al., 2001)... 

Drug Selectivity Partial Agonist Activity Local Anesthetic Action Lipid Solubility Elimination Half-Life Approximate Bioavailability... 

Table 3.1 The elimination half life for selected drugs ...

The selection of an equation (either Eq. 10.15 or Eq. 10.17) to determine the loading dose of a drug, by comparison, solely depends upon the available information. Equation 10.15 requires the knowledge of the apparent volume of distribution of the drug and the desired plasma concentration. Equation 10.17 requires knowledge of the infusion rate necessary to maintain the desired plasma concentration of the drug and of the elimination half life of the drug. 

Select the dosing interval (it is a safe and good practice to start with a dosing interval equal to the drug s elimination half life). 

From calculations provided here, it is accurate to state that the failure to follow the dosage regimen (prescribed dose at a prescribed dosing interval) of a drug can result in serious consequences. Therefore, it is important that patients in your pharmacy, and/or a family member, follow the prescribed directions scmpulously, particularly for drugs that manifest a narrow therapeutic range and a long elimination half life. From your pharmacy experience, you may be aware that some patients tend to take selected... 

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