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- systems biology; modelling; differential equations; metabolism; nutrition; bovine; fertility; reproduction; hormones; follicles; Dexamethasone; PK-PD (1) (remove)
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We present a mechanistic pharmacokinetic-pharmacodynamic model to simulate the effect of dexamethasone on the glucose metabolism in dairy cows.
The coupling of the pharmacokinetic model to the pharmacodynamic model
is based on mechanisms underlying homeostasis regulation by dexamethasone.
In particular, the coupling takes into account the predominant role of dexamethasone in stimulating glucagon secretion, glycogenolysis and lipolysis and in
impairing the sensitivity of cells to insulin. Simulating the effect of a single
dose of dexamethasone on the physiological behaviour of the system shows that
the adopted mechanisms are able to induce a temporary hyperglycemia and
hyperinsulinemia, which captures the observed data in non-lactating cows. In
lactating cows, the model simulations show that a single dose of dexamethasone
reduces the lipolytic effect, owing to the reduction of glucose uptake by the
mammary gland.