Steady-state plasma concentration versus time plot

Pharmacokinetic Analysis. Standard noncompartmental analyses were conducted to assess ATI and ATF pharmacokinetics using WinNonlin software (v. 2.1) (Pharsight, Mountain View, CA). The areas under the plasma concentration versus time curve from time zero to inhnity (AUCint) were determined via the log-linear trapezoidal method. The terminal half-life was determined from the relationship of ti/2 = In 2/, where k is the negative slope of the terminal phase of the InC versus time plot. Systemic clearance (CL) was estimated by dividing the administered dose by AUCint. The volume of distribution at steady state (Vss) was determined by the product of clearance and the mean residence time. 

Figure 11.10 Plasma concentration (Cp) versus time plot illustrating high (a) and low (b) fluctuation () values following the attainment of the steady-state condition, min, minimum max, maximum MTC, minimum toxic concentration MEC, minimum effective concentration.

In support of inhalation studies, blood samples are taken after a 4- to 6-hour whole-body or nose-only exposure period. The steady-state plasma concentration and the elimination rate are determined. The steady-state concentrations are plotted versus exposure concentration to make the determination of dose proportionality. A kinetic model is developed and used to predict steady-state concentrations and the time to reach steady state. 

Figure 10.17 Plasma concentration (Cp) versus time during and post-infusion (rectilinear plot).7, time of cessation of infusion f, time since the infusion was stopped ss, steady state.

Plot the difference between the steady-state plasma concentration and the observed plasma concentration in Table 10.4 (i.e. (Cp)ss — (Cp)obs) versus time on semilogarithmic paper (values... 

---