Non-Linear Pharmacokinetics Explained
β’Download as PPTX, PDFβ’
10 likesβ’1,068 views
Non-linear pharmacokinetics occurs when some aspect of a drug's absorption, distribution, metabolism, or excretion is saturable at higher doses. This can be caused by saturation of enzymes involved in drug metabolism or transporters involved in absorption. The Michaelis-Menten equation can be used to describe non-linear kinetics, where Vmax is the maximum rate and Km is the substrate concentration at half Vmax. Km and Vmax can be estimated from plasma concentration-time data after IV administration or by plotting steady-state concentration against dosing rate. Non-linear kinetics is usually due to saturation of protein binding, hepatic metabolism, or renal transport of the drug.
Recommended
Recommended
More Related Content
What's hot
What's hot (20)
Similar to Non-Linear Pharmacokinetics Explained
Similar to Non-Linear Pharmacokinetics Explained (20)
More from SUJITHA MARY
More from SUJITHA MARY (20)
Recently uploaded
Recently uploaded (20)
Non-Linear Pharmacokinetics Explained
- 1. 1 NON-LINEAR PHARMACOKINETICS PRESENTED BY SUJITHA MARY MPHARM PHARMACEUTICS ST JOSEPH COLLEGE OFVPHARMACY
- 2. 2 CONTENTS:- β’ Causes of non-linearity β’ Michaelis menten equation β’ Estimation of π² π πππ π½ πππ β’ Conclusion β’ Reference
- 3. 3 NON-LINEAR PHARAMACOKINETICS β’ It is a Dose Dependent Pharmacokinetics. β’ Non-Linear pharmacokinetics models imply that some aspect of the pharmacokinetic behaviour of the drug is saturable.
- 4. 4 CAUSES OF NON-LINEARITY:- β’ Saturation of enzyme in process of drug ADME β’ Pathologic alteration in drug ADME
- 5. 5 CAUSES DRUG When absorption involves carrier mediated transport systems Riboflavin, ascorbic acid When presystemic gut wall or hepatic metabolism attains saturation Propranolol When absorption is solubility or dissolution rate limited Griseofulvin, GI absorption
- 6. 6 Distribution CAUSES DRUG Saturation of binding sites on plasma protein Phenylbutazone Saturation of tissue binding sites Thiopental
- 7. 7 Drug Metabolism CAUSES DRUG Capacity limited metabolism due to enzyme and/or cofactor saturation Phenytoin, Alcohol, Theophylline Enzyme induction Carbamazepine
- 8. 8 Drug Excretion CAUSES DRUG Active tubular secretion Penicillin G Active tubular reabsorption Water-soluble vitamins, glucose
- 9. 9 MICHAELIS MENTEN EQUATION β’ Non linear pharmacokinetics can be best described by michaelis menten equation. β π πͺ π π = π½ πππ πͺ π² π + πͺ Where: o -dC/dt = Rate of decline of drug concentration with time. o Vmax = Theoretical maximum rate of the process. o Km = Michaelis-Menten constant.
- 10. 10 1. When π² π= C β π πͺ π π = π½ πππ π 2. When π² π ΛΛ C β π πͺ π π = π½ πππ πͺ π² π 3. When π² π ΛΛ C β π πͺ π π = π½ πππ
- 11. 11 Estimation of Km and Vmax :- β’ The parameters π² πand π½ πππ can be assessed from the plasma drug concentration time data collected after i.v. bolus administration of the drug with non-linear elimination characteristics. β π πͺ π π = π½ πππ πͺ π π² π + πͺ π (π) β’ Integration of above equation π₯π¨π πͺ = π₯π¨π πͺ π + (πͺ π β πͺ) π. ππππ² π β π½ πππ π. ππππ² π (π)
- 12. 12 A semi log plot of C versus t yields a curve with a terminal linear portion having slope β π½ πππ π. ππππ² π and when back extrapolated to time zero gives y- intercept πππ πͺ π . ππππͺ = πππ πͺ π β π½ πππ π. ππππ² π (π)
- 13. 13 At low plasma concentrations, equation (2) and (3) are identical. Equating the two and simplifying further, we get: (πͺ π β πͺ) π. ππππ² π = πππ πͺ π πͺ π (π) Km Can thus be obtained from above equation. Vmax Can be computed by substituting the value of Km in the slope value.
- 14. 14 π² π πππ π½ πππ from steady state concentration:- When a drug is administered as a constant rate i.v. infusion or in a multiple dose regimen, the steady-state concentration Cssis given in terms of βdosing rateβ DR as: π«πΉ = πͺ πΊπΊ πͺπ π» (π) Where DR= R0when the dose is administered as zero order i.v. infusion and it is equal to FX0/Ο when administered as multiple dosage regimen (F is fraction bioavailable, X0is oral dosage and Ο is dosing interval).
- 15. 15 At steady state, the dosing rate equals rate of decline in plasma drug concentration and if the decline (elimination) is due to a simple capacity limited process (for e.g. metabolism), then; π«πΉ = π½ πππ πͺ πΊπΊ π² π+πͺ πΊ (2) A plot of CSS versus DR yields a typical hockey-stickshaped curve as shown in figure:
- 16. 16 β’ The rate process of drugβs ADME are depends upon carrier or enzyme that are substrate specific, have definite capacities and are susceptible to saturation at a high drug concentration β’ Nonlinear kinetics is usually due to saturation occuring in one of the pharmacokinetic mechanisms: protein binding, hepatic metabolism, or active renal transport of the drug. CONCLUSION:-
- 17. 17 REFERENCE:- β’ D M Brahmankar, Sunil B. Jaiswal, Biopharmaceutics and pharmacokinetics, 3rd edition, Delhi, Vallabh Prakashan, 2015, p. 307-317