Bioequivalence and Bioavailability Forum

Hi intuitivepharma,

as promised some thoughts.

Fitting your data (assuming a dose of 100 units) I got:
V/F  1.0417028
K01  0.69324023
K10  0.027723077
Tmax 4.8370075
To keep it simple I would set the sampling interval to multiples of 15 minutes. We should have at least three sampling time points in the absorption phase and around C_max (FDA). So I suggest to aim for five evenly spaced samples in the interval [0, 4.75] ⇒ [0, 0.95, 1.9, 2.85, 3.8, 4.75] ⇒ mround(t,0.25) ⇒ [0, 1, 2, 2.75, 3.75, 4.75]. The remaining ten sample geometrically spaced, rounded ⇒ [6.5, 8.75, 11.75, 16, 21.5, 29, 39.25, 53.25, 72].

Let’s see:





Smaller partial derivatives for K10 would be nice.
           schedule 1  schedule 2
∑ last 6:    -6295       -6671
∑ last 5:    -4612       -4639
OK, we can expect to obtain more reliable fits in schedule 2. Since C_max is higher variable than AUC it would be a good idea to sample more often in the earlier part of the profile. FDA’s 3/3-recommendation gives too few samples in most cases. Play around with the schedules, but forget modeling – is not helpful. Concentrate on clinical practicability.