2013B12 Explain how the differences in pharmacokinetics of alfentanil and fentanyl can influence the way
they are administered intravenously.

Fentanyl

Alfentanil

Implication

-Lipid solubility

600x

90x

May partly account for V_DSS FENT >> ALF

-pKa (both weak bases)

8.4

6.5

-% unionised at pH 7.4

9%

89%

Main reason for ALF’s short time to peak effect (TTPE)

Offsets lower lipid solubility

-%Plasma protein bound

83%

90%

-V_DC (L/kg)

0.2

?

-V_DSS (L/kg)

4

0.6L/kg

FENT faster offset if short infusion

ALF faster offset if long infusion

-t_1/2ke0 (mins)

6.9

0.9

ALF: high % unionised offsets low LS

-t_1/2α (mins)

1 fast, 18 slow

1 fast, 14 slow

Both rapid offset after single bolus

Fentanyl

Alfentanil

Implication

Metabolism

Liver. CYP3A4 > other

Liver. CYP3A4,5

Metabolites

Inactive

Norfentanyl > other

Inactive

Noralfentanil > other

Both safe in renal failure

Cl (mL/kg/min)

13

6

t_1/2β (mins)

190-475

70? 100?

Note ALF ↓Clearance but ↓↓V_DSS

t_1/2β = V_D/Cl x log_e2

Hence offset after long infusion ALF >> FENT

Excretion

Metabolites -> urine

Metabolites -> urine

Fentanyl

Alfentanil

Implication

-Onset (time to 80%) (mins)

3

1.2

Alfentanil for brief intense stimulation

e.g. laryngoscopy

e.g. lancing peri-anal abscess.

Fentanyl for medium to long duration surgery

e.g. lap cholecystectomy

e.g. CABG

-TTPE (mins)

5

1.8

-Duration (mins)

10 (highly dose-dependent)

4

Graph

Difference

·  <2 hours: fentanyl’s CSHT is shorter

o Large VDSS, moderate clearance rate

o Suited to bolus or short infusion

o Can administer large bolus for prolonged effect (e.g. CP bypass)

·  >2 hours: alfentanil’s CSHT is shorter

o Very low VDSS, low clearance

o Suited to bolus and/or variable length infusion (?)