Extravascular administration peak plasma concentration

Figure 6.16 Rectilinear plots of plasma concentration (Cp) against time following the administration of a drug via extravascular route. The accuracy of the estimation of the peak plasma concentration (Cp)max depends upon having sufficient data points (full points) to identify the time of peak concentration (fmaj.

Figure 7.15 represents plasma concentration versus time data following the administration of an identical dose of a drug by intravascular or extravascular routes. The absorption of drug from the extravascular route can be described as slow but virtually complete. Since peak time is long and peak plasma concentration is much lower than the initial plasma concentration for an intravenous bolus, this can be attributed to slower absorption. The (AUC)q for the intravascular and extravascular routes may be identical. If this assumption is applicable, then the extent of drug absorption is identical. 

At 0 and >, X = 0 and Cp = 0 and at t= tmax (i e. peak time), X = (A)max and Cp = (Cp)max (i.e. peak plasma concentration or highest plasma concentration). Please note the difference between intra- and extravascular routes of drug administration with regard to the time at which the highest, or peak, plasma concentration occurs. 

Peak plasma concentration following the administration of a single extravascular dose, or the first dose, is obtained as follows ... 

For example, in Eq. 11.12 (for intravenous bolus), (Cp)o represents the intercept of the plasma concentration versus time profile following the administration of a single dose of a drug. In Eq. 12.13 (for extravascularly administered dose), we can obtain the intercept value from the plasma concentration versus time plot. In both Eqs 11.12 and 12.13, the denominator term is identical (i.e. 1 - For an intravenous bolus, maximum or peak plasma concentration occurs at time 0 and, for an extravascular route, maximum concentration will occur at peak time (Fig. 12.3). 

Methadone is a p receptor agonist with special properties that make it particularly useful as a maintenance agent. Rehably absorbed orally, it does not reach peak concentration until about 4 hours after administration and maintains a large extravascular reservoir (Kreek 1979). These properties minimize acute euphoric effects. The reservoir results in a plasma half-life of 1—2 days, so there are usually no rapid blood level drops that could lead to withdrawal syndromes between daily doses. Effective blood levels are in the range of 200-500 ng/mL. Trough levels of 400 ng/mL are considered optimal (Payte and Khouri 1993). There is wide variability among individuals in blood levels with identical doses (Kreek 1979), and some have inadequate levels even with doses as high as 200 mg/day (Tennant 1987 Tenore 2003). 

Figure 2.2 Plasma IgG levels following i.m. or s.c. injection in humans. This graph, which is redrawn from Figure 1 in [2], shows the difference in IgG uptake following oral administration and subcutaneous, intramuscular, or intravenous injection. In this particular situation, anti-Rh immunoglobulin G (IgG) was injected into the deltoid or subcutaneously in the buttock. Uptake rates were higher for i.m. injection (0.43 0.11 day" ) than for s.c. injection (0.22 0.025 day" ). Peak concentrations, which occurred after 3 days, were higher for i.m. injection ( 40%) than s.c. injection ( 30%). Pharmacokinetic analysis was used to predict average concentrations and rates of equilibration between vascular and extravascular compartments.

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