1. Dosage Regimens II Arthur G. Roberts

2. Question Can a drug have a low therapeutic index and a broad therapeutic window? No therapeutic index= [drug] min,toxicity /[drug] min,effectiveness f(Effectiveness) [drug] Toxicity Therapeutic Window

3. Multiple-Dose Regimens Arthur G. Roberts

5. Dosing Frequency

7. drug p

8. Dosing Frequency 1 2 3 4 5 6 7 8 9 N

9. t dose,N

10. Dosing Frequency drug p, max

11. Dosing Frequency drug p, min

12. Dosing Frequency drug ss, max

13. Dosing Frequency drug ss, min

14. Dosing Frequency f lost1 Only during the initial dose

15. Accumulation Index

16. Phenobarbital 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

17. Phenobarbital Cl (Normalized)=0.035 L/(hr*kg) no active metabolites V d (Normalized)=0.5L/kg dose IV = 30 mg = drug p0 dosing interval = 4 hours number of doses = 4 weight=70 kg Cl,Vd,k,t 1/2,f lost1,drug p,max,drug p,min drug ss,max,drug ss,min,AI induces CYP2C9 (effects?)