Volume of Distribution Prediction: Physiologically Based ...
Volume of Distribution Prediction: Physiologically Based ... Volume of Distribution Prediction: Physiologically Based ...
patrick-poulin@videotron.ca P. Poulin. April, 2007.Distribution Prediction AAPS – November 11, 2009Prediction Methods of Kp (Vdss)PrincipleDrug-SpecificInputsTISSUECOMPOSITION (TC)- Kp’s were calculated as the ratioof the sum of free and bound drug(i.e., nonspecific & specific) in tissuecomponents (intracellular &interstitial spaces) to that in plasma.- Lipophilicity (Log P, Log D)- Plasma proteins binding (fup)- Blood:plasma ratioARUNDEL- Kp’s were calculated from therelationships between Vdss anddisappearance rate constantsobserved in 5 groups of tissues.- Lipophilicity (Log D)- Plasma proteins binding (fup)- Rat Vdss in vivoData - In vitro based (All classes of drugs) - In vivo based (All classes of drugs)Number ofpublishedversions- 4 (Poulin, Krishnan & Theil, 1995-2002)(Rodgers & Rowland, 2007) (GastroPlus®)- 1 (Astrazeneca, 1997)
patrick-poulin@videotron.ca P. Poulin. April, 2007.Distribution Prediction AAPS – November 11, 2009Prediction Methods of Kp (Vdss)CORRELATIONSHYBRIDS &OIE TOZERPrincipleDrug-SpecificInputs- Kp’s were predicted with correlations.- Kp muscle is correlated with Kp ofother lean tissues for in vivo data.- Kp fat is correlated with Kp muscleadjusted for lipophilicity.- Kp in vivo of muscle- Rat Vdss in vivo- Lipophilicity (log P)- Kp’s were predicted with correlations.- Kp of lean tissues and fat (or Vdss)are correlated with in vitro data(blood:plasma PC or physicochem.).- Some Relations with Physiology.- Lipophilicity (Log p)- Plasma proteins binding (fup)- Blood:Plasma ratioData - In vivo based (All classes of drugs) - In vitro based (Basic drugs only)Number ofpublishedversions- 3 (Poulin & Theil 2000) (Bjorkman 2004)(Janssen et al. 2008)- 3 (Poulin & Theil 2009 A,B)(Lombardo 2004)
- Page 1 and 2: AAPSVolume of Distribution Predicti
- Page 3 and 4: patrick-poulin@videotron.ca P. Poul
- Page 5 and 6: patrick-poulin@videotron.ca P. Poul
- Page 7 and 8: patrick-poulin@videotron.ca P. Poul
- Page 9 and 10: patrick-poulin@videotron.ca P. Poul
- Page 11 and 12: patrick-poulin@videotron.ca P. Poul
- Page 13: patrick-poulin@videotron.ca P. Poul
- Page 17 and 18: patrick-poulin@videotron.ca P. Poul
- Page 19 and 20: Additional Validation of this Study
- Page 21 and 22: % WITHIN 2-FOLD ERRORPredictive Per
- Page 23 and 24: % WITHIN 2-FOLD ERRORpatrick-poulin
- Page 25 and 26: patrick-poulin@videotron.ca P. Poul
- Page 27 and 28: patrick-poulin@videotron.ca P. Poul
- Page 29 and 30: Cell permeability (cm/s)Cell permea
- Page 31 and 32: patrick-poulin@videotron.ca P. Poul
- Page 33: ReferencesPoulin P, Theil FP. 2002.
patrick-poulin@videotron.ca P. Poulin. April, 2007.<strong>Distribution</strong> <strong>Prediction</strong> AAPS – November 11, 2009<strong>Prediction</strong> Methods <strong>of</strong> Kp (Vdss)CORRELATIONSHYBRIDS &OIE TOZERPrincipleDrug-SpecificInputs- Kp’s were predicted with correlations.- Kp muscle is correlated with Kp <strong>of</strong>other lean tissues for in vivo data.- Kp fat is correlated with Kp muscleadjusted for lipophilicity.- Kp in vivo <strong>of</strong> muscle- Rat Vdss in vivo- Lipophilicity (log P)- Kp’s were predicted with correlations.- Kp <strong>of</strong> lean tissues and fat (or Vdss)are correlated with in vitro data(blood:plasma PC or physicochem.).- Some Relations with Physiology.- Lipophilicity (Log p)- Plasma proteins binding (fup)- Blood:Plasma ratioData - In vivo based (All classes <strong>of</strong> drugs) - In vitro based (Basic drugs only)Number <strong>of</strong>publishedversions- 3 (Poulin & Theil 2000) (Bjorkman 2004)(Janssen et al. 2008)- 3 (Poulin & Theil 2009 A,B)(Lombardo 2004)
Change language