Bioequivalence and Bioavailability Forum

Hi Martin,

❝ Several guidelines mention that a negative pre-dose corrected value should be set to zero. However, what about subsequent levels?

❝ I think setting also all concentrations after the first negative to zero would make some sense […] this should be also in-line with guidelines as the method for baseline subtraction needs to be specified a-priori.

Well, this is exactly what I have done for ages. never got a deficiency letter.

❝ PS.: premise of stable endogenous could be verified by looking at adjusted concentrations after the first negative (inclusive) adjusted concentration: should be symmetrically distributed around zero.

Really? You explained that to me so may times; excuse my walnut-sized brain. Baseline (C₀) = lognormal. Post-dose (C₁) = lognormal. C₀–C₁ = normal?

C0     <- rlnorm(n=1e6, meanlog=log(1)-0.5*log(0.3^2+1), sdlog=sqrt(log(0.3^2+1)))
C1     <- rlnorm(n=1e6, meanlog=log(2)-0.5*log(0.3^2+1), sdlog=sqrt(log(0.3^2+1)))
C1.adj <- C1-C0
C1.adj[C1.adj < 0] <- 0 # force to zero
mean(C0);sd(C0)/mean(C0)
mean(C1);sd(C1)/mean(C1)
mean(C1.adj);sd(C1.adj)/mean(C1.adj)
summary(C1.adj)
qqnorm(y=C1.adj, col="blue", cex=0.5, las=1)
qqline(y=C1.adj, col="red", lwd=2)