Drug-concentration time curve

Bioavailability is the amount of drug in a formulation that is released and becomes available for absorption or the amount of the drug absorbed after oral administration compared to the amount absorbed after intravenous administration (bioavailability - 100%), judged from areas remaining under plasma drug concentration-time curves. 

In Eq. (3.4), doseiv is the amount of drug administered intravenously, AUC is total area under the drug concentration-time curve, and k is the first-order elimination rate constant... 

Three correlation levels have been defined and categorized in descending order of the ability of the correlation to reflect the entire plasma drug concentration-time curve that will result from administration of a dosage form. The relationship of the entire in vitro dissolution curve to the entire plasma level curve defines the correlation. 

The Drug Delivery Index (DDI) ahows a quantification of the reduction in the drug dose and the systemic exposure observed after drug release specificahy to the colon [37]. It may be calculated using AUC (Area l/nder the plasma drug concentration-time Curve) data or drug concentrations in blood and colonic tissues under steady-state conditions ... 

In the case of metoprolol succinate and metoprolol fumarate, the maximum drug concentration in the plasma( max) and the area under the plasma drug concentration-time curve were statistically equivalent, based on a 90% conLdence interval (Sandberg et al., 1993). With fenoprdffcQmthe following administration of its calcium salt was reached somewhat later thaCmjpassociated with the sodium form (Rubin et al., 1971). This was attributed to the slower dissolution rate for the calcium salt in acidic pH. Bioavailability and the measured distribution and elimination parameters, however, were reported to be similar. 

Cl plasma concentration at time zero fi/2a, distribution half-life f1/2jg, elimination half-life Kej, elimination rate constant from central compartment Ki2/.K2i, transfer rate constant between peripheral and central compartments AUC(o ), total area under plasma drug concentration time curve Vd(area> apparent volume of distribution GB, total body clearance. 

Should an early decision be made to develop the eutomer, then the drug development program would be the same as for conventional NCEs, with the possible exception that assessment of in vitro and/or in vivo chiral inversion may be desirable. However, if development continues with the racemate, time, cost, and staff resource commitments become magnified. For example, a very important variable to consider is spedes differences in enantiomer exposure. Appropriate toxicokinetic studies are advisable in order to assure that, at toxicological doses, the animal species tested have attained suffident plasma concentrations of each enantiomer to support clinical evaluation at therapeutic doses in humans. The enantiomeric ratio (based on maximum drug concentrations fCmax] and/or area under the plasma drug concentration-time curve [ALJC]) should be evaluated, and... 

This may be concentration and drug dependent. t = Increase = decrease — = no effect, k, = absorption rate constant = time AUC = area under the plasma drug concentration time curve. for peak drug concentration in plasma ... 

The mean in vitro dissolution time is compared to either the mean residence time or the mean in vivo dissolution time. Level B correlation, like Level A correlation, uses all of the in vitro and in vivo data but is not considered to be a point-to-point correlation and does not uniquely reflect the actual in vivo plasma level curve, since several different in vivo plasma level-time curves will produce similar residence times. A Level C correlation is the weakest IVIVC and establishes a single point relationship between a dissolution parameter (e.g., time for 50% of drug to dissolve, or percent drug dissolved in two hours, etc.) and a pharmacokinetic parameter (e.g., AUC, Cmax, Tmax). Level C correlation does not reflect the complete shape of the plasma drug concentration-time curve of dissolution profile. 

Because the area under the plasma drug concentration-time curve during a dosage interval at steady-state is equal to the total area under the curve after administering a single intravenous dose, the average plasma concentration at steady-state can be estimated from... 

AUC total area under the plasma drug concentration-time curve (from... 

Figure 7.1 Sample drug-concentration time curve for a single participant of 290 ng/mL and t j of 6 hours)...

Fig. 6.41. Dose/Genotype Relationship A schematic representation of the potential benefit of adjusting drug dose to patient genotype. The theoretical normal drug concentration/time curve is depicted by the dashed line in the concentration/time curves of Patients A-D at the top of the figure while the theoretical genetic drug concentration/time curve for each patient is expressed by the solid line. The allele status for each patient is shown below the theoretical plots. The oval containing the X indicates the presence of the detrimental allelic variation. The extra oval in Patient D indicates duplication of one of the normal alleles. The bar graph at the bottom of the figure indicates the normal doses (shaded) compared to the dose adjustments that should be made based on the patient s allele status (180).

Absolute bioavailability of a drug is the systemic availability of the drug after extravascular administration of the drug and is measured by comparing the area under the drug concentration-time curve after extravascular administration to that after IV administration, provided the and Vd are independent of the route of administration. Extravascular administration of the drug comprises routes such as oral, rectal, subcutaneous, transdermal, nasal, etc. 

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