1. Metabolite Kinetics I Arthur G. Roberts

2. DrugMetabolite Renal Excretion Metabolite of a Metabolite Biliary Excretion keke Options keke keke keke Other Excretion kmkm

3. DrugMetabolite keke kmkm Out or Somewhere Else

4. DrugMetabolite keke kmkm Out or Somewhere Else

5. k e =>k m k m >k e keke kmkm kmkm k e =k m

6. The Brain +++++-----++++++++++++++ -----+++++-------------- Neuron Cl - Na + or K + GABA A receptor (Ligand-gated Ion Channel) GABA Glutamate (Glu) Action potential Glutamate receptor (Ligand-gated Ion Channel) KCC2 (K+/Cl- symporter) (a.k.a. SLC12A5) Na + Voltage-Gated Ion Transporter Na + GABA K + and Cl -

7. Carbamazepine Neuron Cl - Na + or K + GABA A receptor (Ligand-gated Ion Channel) GABA Glutamate (Glu) Glutamate receptor (Ligand-gated Ion Channel) KCC2 (K+/Cl- symporter) (a.k.a. SLC12A5) Na + Voltage-Gated Ion Transporter Na + GABA K + and Cl - X ++++++++++++++++++++++++ ------------------------ Action potential used for seizures and neuropathic pain

8. Carbamazepine oral dose= 1000 mg Bioavailability=100% Protein Binding (CBZ) =75% t 1/2 Carbamazepine (CBZ)=24 hours (repeated dosing) t 1/2 Carbamazepine-10,11-epoxide (CBZ epoxide)=7.4 hours Cl m (CBZ) = 3 L/hr V d (CBZ) =~ V d (CBZ epoxide) k m ?, k e ?,V d ?,Cl int ?,E?,Cl b ? and Cl h ?

9. AUC AUC e

10. Metabolite formed

11. Excretion Rate DrugMetabolite keke kmkm Out or Somewhere Else

12. Carbamazepine oral dose= 1000 mg Bioavailability=100% Protein Binding (CBZ) =75% t 1/2 Carbamazepine (CBZ)=24 hours (repeated dosing) t 1/2 Carbamazepine-10,11-epoxide (CBZ epoxide)=7.4 hours Cl m (CBZ) = 3 L/hr V d (CBZ) =~ V d (CBZ epoxide) AUC m ?, AUC e ?, metabolite total ? f metabolite, metabolite excretion rate?