Highly variable drugs values

Absolute bioavailability this implies a comparison of plasma levels after oral and i.v. administration of the drug. Most psychotropic drugs have a good bioavailability, i.e. values between 30 and 100%. Low bioavailabilitv, as seen with buspirone, is associated with highly variable drug plasma concentrations and is not a desirable feature of a drug... 

Subject variability High intraindividual variability in QTc values (circadian and seasonal variation law of regression to the mean) High interindividual variability in QTc values (males versus females) Unknown prevalence in the general population of subjects carrying silent mutations in the ion channels responsible for cardiac repolarization (these subjects have normal QTc value but reduced repolarization reserve) Variability in the individual metabolic capacity for a given drug... 

There is substantial variability in the pharmacokinetics of vinblastine in patients. Evidence has been obtained that implicates altered liver function and dose-dependent elimination as contributing factors to the variable pharmacokinetics. When vinblastine was administered by a bolus injection, a mean terminal elimination half-life of 29.2 hr was estimated for a group of 24 patients, but the half-lives ranged from a low value of 16 hr to a high value of 65 hr (55). When vinblastine was administered by intravenous infusion, clearance of the drug appeared to decrease with time over a 4-month period decreases in serum albumin values were found to be correlated with decreases in the clearance of vinblastine. 

For the new compound as victim, in vitro data to predict L by the enzyme that is affected is what is critical to determine an accurate prediction. Bona fide values for fci, are hard to obtain, even for well established drugs. At best, values are estimates and intersubject variability in the term probably overwhelms any investment in attempts to gain highly precise values. However, it is important to note that the sensitivity of the prediction of DDI increases markedly as the value of the/cl exceeds 0.9 (Figure 8.4). 

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