Fig. 2.

A schematic overview of the major concepts to build our NODE for PK. The first step towards our NODE for PK is to reduce autonomous (time-independent right-hand side) multi-dimensional ODE systems to a non-autonomous (time-dependent right-hand side) one-dimensional system since the general NODE should be applicable without mechanistic assumptions. The second step is to substitute the right-hand side of an ODE with an NN. In a third step, the concentration variable and time variable were separated into two NNs with one-dimensional input and output. In a fourth step, generally known structures such as drug administration with absorption process can be included in the NODE. In a fifth step, the NODE can optionally be combined with a known mechanistic part, if prior knowledge is available