Extravascular administration peak time

Please note that since peak time is independent of the dose administered, for a 500 mg tablet, the peak time will be identical (i.e. 0.971 h or 58.25 min). However, if an identical dose or even a different dose of procainamide is administered through a different extravascular route (e.g intramuscular), different dosage form (e.g. solution, capsule, controlled release tablet) or different formulation (e.g. tablet made by a different manufacturer or the same manufacturer with a different formulation), the peak time may be different. This is because the absorption rate constant may change with route of administration, dosage form and formulation. 

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. 

The peak time following the administration of a single extravascular dose is obtained by employing the following equation (equivalent to Eq. 6.15) ... 

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). 

Figure 6.14 Rectilinear plots of plasma concentration (Cp) against time following the administration of on identical dose of a drug via the oral or intramuscular (IM) extravascular routes to show variation in time to peak concentration (tmaxi orid in onset of action. MTC, minimum toxic concentration MEC, minimum effective concentration.

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