The initial sample size of the present study is calculated from the difference of minimum plasma concentration of nevirapine between the two groups of patients [ 12].
A graphical analysis of the relationship between average plasma concentration (Cavg), minimum plasma concentration (Cmin), and effective constant concentration (ECC = the constant concentration giving the same average viral inhibition as the time varying concentration) demonstrated, not unexpectedly, that they were highly correlated (data not shown).
30 In addition, similar dose-normalized minimum plasma levels were noted between the two formulations (0.44 ng/mL/mg vs 0.45 ng/mL/mg).
Plasma concentration of MK-2206 was used to determine pharmacokinetic parameters, including the peak plasma concentration (Cmax), time to maximum concentration, minimum plasma concentration, and area under the concentration time curve (AUC), as described previously by Yap and colleagues [ 13].
The minimum required plasma dilution of 1 20 was determined based on the potential for interference by known plasma components such as inter-α-inhibitor (34).
It was suggested that there may be a minimum plasma drug concentration (between 0.5 and 1 ng/ml [ 19] for optimal anthelmintic activity against susceptible gastrointestinal or lung nematodes. However, the existence of such a minimum effective concentration has not been confirmed.
IDV PK parameter estimates included area under the plasma-concentration-time curve from time 0 to 8 hours after the dose, (AUC0 8 hrs), maximum plasma concentration (Cmax), minimum plasma concentration (Cmin), and time to maximum plasma concentration (Tmax).
Although minimum plasma concentration of nevirapine is somewhat different during the early period of ART between the two subgroup patients as mentioned, the long-term antiviral responses between these two groups were not different as demonstrated in the present study.
17, 18 In addition, switching between topiramate formulations did not affect steady-state exposure, including minimum plasma topiramate concentrations, suggesting that at equivalent total daily doses, USL255 will maintain topiramate concentrations at or above the minimum concentrations provided by TPM-IR.
For example, it is very difficult to determine if the observed efficacy is driven by maximum plasma concentration (C max) or minimum plasma concentration (C min) when such a steep drop of DCU plasma exposure is encountered [14].
