Which of the following creates nonlinearity in drug distribution and not in drug absorption?(a) When absorption is solubility or dissolution rate-limited(b) When absorption involves carrier-mediated transport systems(c) When a presystemic gut wall or hepatic metabolism attains saturation(d) Saturation of binding sites on plasma proteinsI have been asked this question in an international level competition.My doubt stems from Non Linearity of Drugs in chapter Compartment Modelling, Non Linear Pharmacokinetics, Bioavailability and Bioequivalence of Drug Biotechnology

Which of the following creates nonlinearity in drug distribution and n

1.	Which of the following creates nonlinearity in drug distribution and not in drug absorption?(a) When absorption is solubility or dissolution rate-limited(b) When absorption involves carrier-mediated transport systems(c) When a presystemic gut wall or hepatic metabolism attains saturation(d) Saturation of binding sites on plasma proteinsI have been asked this question in an international level competition.My doubt stems from Non Linearity of Drugs in chapter Compartment Modelling, Non Linear Pharmacokinetics, Bioavailability and Bioequivalence of Drug Biotechnology
Answer» Right OPTION is (d) Saturation of BINDING sites on plasma proteins To elaborate: Nonlinearity in DRUG absorption can ARISE from 3 important sources these are when absorption is solubility or dissolution rate-limited, when absorption involves carrier-mediated transport systems and when presystemic gut wall or hepatic metabolism attains saturation. Nonlinearity in drug distribution occurs when saturation of binding sites on plasma proteins or saturation of tissue binding sites.

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