Michaelis-Menten absorption kinetics in drugs: - examples and implications.

It is shown that the absorption of phenylbutazone, naproxen, and chlorthiazide is governed by a dose limiting mechanism. This dose dependency may be explained by a saturation absorption process mathematically obeying Michaelis-Menten type kinetics. Observed dose relationships for tetracycline, fenclozic acid and related compounds, phenytoin, and possibly digoxin and digitoxin may be explained if a saturable process in absorption is postulated. This behavior may be produced by insolubility of the drug compound, a limited "window of absorption" in the gastrointestinal tract, or a capacity limited absorption because of the carrier or the transport mechanism involved. The need for suitably designed dose response studies with new drug compounds is discussed.