Search the PBPK Model Repository

  Absorption Model

• First-Order

  Volume of Distribution

• Minimal PBPK (User input Vss)

  Route of Elimination

• Renal clearance (90%); non-specific hepatic metabolism (10%)

  Perpetrator DDI

• None

  Validation

• Four clinical studies describing single and multiple dose exposure of sulfadoxine were used to verify the PBPK model. In comparison of predicted vs. observed AUC, 100% of the studies were within 2-fold and 75% were within 1.5-fold. 

  Limitations

• In the absence of adequate data on the metabolism and excretion of sulfadoxine, it was assumed that 90% was cleared renally and 10% was metabolized by the liver.

  Updates in V19

• Updated in vitro­ data
  • LogP: 4.22 -> 0.54

  Absorption Model

First-Order

  Volume of Distribution

Minimal PBPK (Method 1)

  Route of Elimination

CYP3A4 (fm = 0.50); renal clearance (fe = 0.1)

  Perpetrator DDI

• CYP2D6 Inhibitor

  Validation

• Three clinical studies describing Quinine PK were identified for model verification.
• Three clinical DDI studies where quinine was the victim of CYP-mediated DDIs were used to verify the PBPK model.  All studies were well recovered with simulated Cmax and AUC GMRs within 1.5-fold of the observed

  Limitations

• The Simcyp quinine PBPK model was able to recover interactions CYP3A inducers and inhibitors with reasonable accuracy.
• Verification needed for perpetrator DDI assessment as literature data is unavailable at this time.

  Updates in V19

• Updated in vitro­ data
  • fup: 0.199 -> 0.37
  • Caco-2 A -> B Permeability: 70 x 10-6 cm/s -> 39 x 10-6 cm/s
  • Propranolol reference Permeability: 101 x 10-6 cm/s -> 45 x 10-6 cm/s
• Minimal PBPK with Vss predicted through Method 1
  • Updated retrograde clearance