Dosage Regimens II

Arthur G. Roberts

Question

• Can a drug have a low therapeutic index and a broad therapeutic window? No

• therapeutic index= [drug]min,toxicity/[drug]min,effectivenessf(E

ffecti

vene

ss)

[drug]

Toxicity

Therapeutic Window

Multiple-Dose Regimens

Arthur G. Roberts

Dosing Frequency

Dosing Frequency

Dosing Frequency

drugp

Dosing Frequency

12

34 5 6 7 8 9

N

Dosing Frequencytdose,N

Dosing Frequency

drugp, max

Dosing Frequency

drugp, min

Dosing Frequencydrugss, max

Dosing Frequency

drugss, min

Dosing Frequency

flost1

Only during the initial dose

Accumulation Index

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

Phenobarbital

• Cl (Normalized)=0.035 L/(hr*kg)• no active metabolites• Vd (Normalized)=0.5L/kg

• dose IV = 30 mg = drugp0

• dosing interval = 4 hours• number of doses = 4• weight=70 kg• Cl,Vd,k,t1/2,flost1,drugp,max,drugp,min

• drug ss,max,drugss,min,AI• induces CYP2C9 (effects?)