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Clearance: basic concept (in vitro)

Clearance: basic concept (in vitro). Update OCT 2010. Clearance: definition. Clearance = = Clearance = =. mass x T -1 mass x V -1. Rate of elimination driving concentration. = V x T -1. dx /dt driving concentration.

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Clearance: basic concept (in vitro)

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  1. Clearance: basic concept (in vitro) Update OCT 2010

  2. Clearance: definition Clearance = = Clearance = = mass x T-1 mass x V-1 Rate of elimination driving concentration = V x T-1 dx /dt driving concentration Amount/Time concentration

  3. Clearance : from in vitro to in vivo

  4. In vitro clearance cell dx/dt analyte Driving concentration = constant intrinsic dx/dt Cst Clearance = = Volume of the solution totally cleared by time unit = operational definition

  5. Clearance: in vitro vs. in vitro Taking into account the analyte input analyte (Cin) ° (Cout) Q • Limiting factors • analyte supply = Q x (Cin) • capacity of the system to clear: Clint °

  6. Clearance : in vitro vs in vivo • In vitro analyte Diffusion analyte • In vivo ° Flow (Q) Diffusion

  7. Clearance: general model o Q x Cin o Q x Cout o Q x (Cin - Cout) dX /dt [Cin - Cout] o o Cl = = Q x = Q x E Cin Cin (Driving concentration) extraction coefficient (ratio) flow

  8. Clearance: general model Clorgan = Qorgan x Eorgan Flow Floworgan organism organism organism extration ratio (0 to 1) no unit organism Cl is the blood (plasma) volume which is totally cleared of the drug for a time unit. Clearance is expressed in terms of flow which makes its interpretation difficult for a clinician

  9. Relevance of the clearance concept • Quantifies elimination • Is usually constant ( a parameter) • Parameter controlling exposure (AUC)

  10. Relevance of the clearance concept • For its usefulness • e.g.: dose computation • For its mechanistic value • understanding of mechanism

  11. Application of the clearance concept 1. To the whole body • plasma clearance (body, blood) 2. To a specific organ • liver / kidney / others 3. in vitro systems • hepatocytes (extrapolation from in vitro to in vivo)

  12. Application of the clearance concept • Classification of clearances (Cl) By organ • liver : Clh • kidney : Clr By mechanism • metabolic clearance (Clh) • excretion clearance (Clr) With respect to the matrix fluid • blood • plasma

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