Pharmacokinetics 7

Question 1

Dosage Regimens / intervals

Answer 1

• What are the therapeutic goals? Often vaires by drug
  
  • avoid therapeutic failure due to decreased concentrations
  • Avoid toxicity due to increased concentration
  • Avoid toxicity due to failure to have a drug free interval
  • Decrease time to therapeutic concentrations
• Compliance:
  
  • Pill a cat 4 times daily for life - not likely to happen

Question 2

Multiple Dose Regimens

Answer 2

• Pyelonephritis with urotliths -bladder stone, and inflammation in kidneys
• Treat in hospital with IV administration, then send home
• Send home treatment
• Amoxicillin 66mg/kg per day (normal oral dose)
  *

Question 3

Therapeutic Goal

Answer 3

Maintain drug above the MIC for the entire dosing interval

Question 4

Multiple Dose regimens:

Cmax

Answer 4

1. With a constant Total Daily Dose, splitting the total daily dose into multiple administrations to 4 times a day decreases the Cmax
2. With a constant Total Daily Dose, combining the total daily dose into fewer administrations increases the Cmax

• Efficacy for some drugs is achieved by hitting a targeted Cmax
• Adverse effects for some drugs are associated with Cmax
• Do you want a high Cmax or do you want to avoid a high Cmax?
  
  • it depends

Question 5

Multiple Dose Regimens:

Cmin

Answer 5

1. With a constant Total Daily Dose, splitting the total daily dose into multiple administrations increases the Cmin
2. With a constant Total Daily Dose, combining the total daily dose into fewer administrations decreases the Cmin

• Efficacy for some drugs is achieved by maintaining concentrations above a targeted minimum concentration
• Adverse effects for some drugs are associated with maintaining concentrations above a targeted Cmin
• Do you want to maintain concentrations above a Cmin or do you want them to fall below a Cmin?
  
  • it depends

Question 6

Multiple Dose Regimens:

Css

Answer 6

• Concentration for Steady state remains constant with a constant total daily dose
• However the variability in plasma concentration can be markedly altered by how that dose is administered
• Difference between Cmax and Cmin at steady state - peaks and troughs
  *

Question 7

Multiple doses and drug accumulation

Answer 7

Multiple doses result in a predictable accumulation, just like a CRI, if the subsequent doses are administered within 3-5 half lives of the first dose

The extent of the accumulation is predictable if the dosing interval and T_1/2 are known