logging in or signing up NON COMPARTMENTAL ANALYSIS deepthikompella Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: Embed: Flash iPad Copy Does not support media & animations WordPress Embed Customize Embed URL: Copy Thumbnail: Copy The presentation is successfully added In Your Favorites. Views: 1982 Category: Science & Tech.. License: All Rights Reserved Like it (0) Dislike it (0) Added: July 10, 2011 This Presentation is Public Favorites: 4 Presentation Description an easy way to learn pharmacokinetics Comments Posting comment... By: ksdeepak31 (14 month(s) ago) its a very good one can you allow me to download it Saving..... Post Reply Close Saving..... Edit Comment Close By: mounireddy (16 month(s) ago) can u send me a copy plzz Saving..... Post Reply Close Saving..... 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The 2 major approaches are Model approach Model independent approach ( non compartmental analysis)METHODS FOR ANALYSIS OF PHARMACOKINETIC DATA: MODEL APPROACH MODEL INDEPENDENT APPROACH COMPARTMENTAL MODEL PHYSIOLOGICAL MODEL DISTRIBUTED PARAMETER MODEL MAMMILLARY MODEL CATENARY MODEL PERFUSION LIMITED MODEL DIFFUSION LIMITED MODEL NON COMPARTMENTAL ANALYSIS METHODS FOR ANALYSIS OF PHARMACOKINETIC DATADeficiencies of compartmental analysis: : Deficiencies of compartmental analysis: Lack of meaningful physiological basis for derived parameters. Lack of rigorous criteria to determine # of compartments necessary to describe disposition. Lack of ability to elucidate organ specific elimination. Inability to relate derived parameters to quantifiable physiological parameters. Inability to predict impact of pathophysiology. Inability to provide insight into mechanism of drug-drug and drug-nutrient interactions. Highly sensitive to sampling frequency.NON COMPARTMENTAL ANALYSIS: NON COMPARTMENTAL ANALYSIS Also called as model independent method Doesn't require the assumption of specific compartment model to calculate the pharmacokinetic parameters. Based on assumption that drugs/metabolites follow linear kinetics. Thus it can be applied to any compartmental model: ADVANTAGES: Ease of derivation of pharmacokinetic parameters by simple algebraic equations. The same mathematical treatment can be applied to almost any drug/metabolite provided they follow 1 st order kinetics. A detailed description of drug disposition characteristics is not required. DISADVANTAGES: It provides limited information regarding the plasma drug concentration –time profile. More often it deals with averages. The method doesn't adequately treat non-linear cases.APPLICATIONS:: APPLICATIONS : Non compartmental analysis is used to estimate MRT,MTT,MAT Bioavailability Clearance Apparent volume of distribution Half-life Fraction of drug eliminated from bodyKey terms:: Key terms: MEAN RESIDENCE TIME : The average total time molecules of a given dose spend in the body before being eliminated out. MEAN TRANSIT TIME : The average time molecules of a given dose spend in the kinetic system. MEAN ABSORPTION TIME : The time taken for the drug to appear in systemic circulation. When determined after non-instantaneous administration, the MTT =MRT + MAT After I.V.bolus dose, MRT=MTTMEAN RESIDENCE TIME:: MEAN RESIDENCE TIME : STATISTICAL MOMENT: : : A mathematical description of a discrete distribution of data. Statistical moments calculated from a set of conc.-time data represent an estimate of true moment. MRT Mean residence time = MRT= first moment/zero momentSlide 10: AUC AUMCAREA DETERMINATION : AREA DETERMINATION A. Integration of Specific Function B. Numerical Integration Linear trapezoidal Log trapezoidal Extrapolation to infinity A. Integration of Specific Function Must elucidate the specific function Influenced by the quality of the fit B. Numerical Integration : B. Numerical Integration 1.LINEAR TRAPEZOIDAL :1.Linear trapezoidal : 1.Linear trapezoidal Advantages: Simple (can calculate by hand) Disadvantages: Assumes straight line btwn data points If curve is steep, error may be large Under or over estimate depends on whether curve is ascending of descending2.Log trapezoidal : 2.Log trapezoidal Advantages: Hand calculator Very accurate for mono-exponential Very accurate in late time points where interval btwn points is substantially increased Disadvantages: Limited application May produce large errors on an ascending curve, near the peak, or steeply declining polyexponential curveIN GENERAL:: IN GENERAL: Where = 2.303 x K eSlide 16: 16 Time (hr) C (mg/L) 0 2.55 1 2.00 3 1.13 5 0.70 7 0.43 10 0.20 18 0.025 AUC Determination Area (mg-hr/L) - 2.275 3.13 1.83 1.13 0.945 0.900 Total 10.21 AUMC Determination C x t (mg/L)(hr) 0 2.00 3.39 3.50 3.01 2.00 0.45 Area (mg-hr 2 /L) - 1.00 5.39 6.89 6.51 7.52 9.80 37.11Slide 17: 17Systemic availability: : Systemic availability: The fraction of administered drug that reaches the systemic circulation. Commonly used to measure the extent to which drug is available in the body after non-intravenous administration.CLEARANCE: CLEARANCE Total (systemic) Clearance:Additivity of clearance: : Additivity of clearance: Rate of elimination = Rate of Renal Excretion + Rate of Hepatic Metabolism Dividing removal rate by incoming concentration: Total Clearance = Renal Clearance + Hepatic Clearance CL T = CL R + CL HSlide 21: 100 mg drug administered to a volunteer resulted in 10 mg excreted in urine unchanged:APPARENT VOLUME OF DISTRUBUTION:: APPARENT VOLUME OF DISTRUBUTION : Calculation via moment analysis Vss = CL*MRT If administration via a short term infusion: K 0 = infusion rate T = infusion durationHALF LIFE: HALF LIFE If drug declines via monoexponential decline MRT=AUMC = C 0 /K 2 = 1 AUC C 0 /K K MRT I.V = 1/K t1/2 = 0.693* 1 k t1/2= o.693 * MRT I.V: Extraction Ratio: : : Extraction Ratio: Ratio of the rate of xenobiotic elimination and the rate at which xenobiotic enters the organ.CONCLUSION:: CONCLUSION: This overview of noncompartmental methods based on statistical moment theory permits a wide range of analysis, that in most instances, will be adequate to characterize the pharmacokinetics of a drug. There are ofcourse,certain limitations like Nonlinear events are not adequately treated by SMT. Also SMT provides only limited information regarding time course of drug concentration ( averages are considered). You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.