3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.3. Pharmacology
                  3.1.3.5. Opioids
                      3.1.3.5.3. Opioid agonists
 3.1.3.5.3.2. Pharmacokinetics of opioids 

Pharmacokinetics

[SH4:p87-p90,p93-p102]

Distribution (Vd and protein binding)

 

Distribution [SH4:p93] or [RDM6:p401]
Vd (steady state) Protein binding Comment

Morphine

3.0 - 5.0 L/kg 35% (20 - 40%)
Pethidine 3.0 - 5.0 L/kg 70%
Fentanyl 3.0 - 5.0 L/kg 84%
Sufentanil 2.5 - 3.0 L/kg 93%
Alfentanil 0.4 - 1.0 L/kg 92% Smaller Vd than fentanyl due to higher protein binding and lower lipid solubility
Remifentanil 0.2 - 0.3 L/kg 66-93% (80% ?)

Metabolism (Hepatic extraction ratio and clearance)

Metabolism [RDM6:p401]
Hepatic extraction ratio Clearance Comment
Morphine 0.6 - 0.8 15 - 30 mL/kg/min
Pethidine 0.5 - 0.7 8 - 18 mL/kg/min
Fentanyl 0.8 - 1.0 10 - 20 mL/kg/min
Sufentanil 0.7 - 0.9 10 - 15 mL/kg/min
Alfentanil 0.3 - 0.5 4 - 9 mL/kg/min
Remifentanil N/A 30 - 40 mL/kg/min

Action profile (half-times)

 

Action profile [SH4:p93]
Elimination T1/2 Context sensitive T1/2 (4 hours) Effect-site equilibration time Comment
Morphine 1.7 - 3.3 hours
Pethidine 3 - 5 hours
Fentanyl 3.1 - 6.6 hours 260 min 6.8 min
Sufentanil 2.2 - 4.6 hours 30 min 6.2 min

Compared with alfentanil, sufentanil has longer half-time but shorter context-sensitive half-time

Alfentanil 1.4 - 1.5 hours 60 min 1.4 min Short equilibration time due to lower pK (thus higher degree of non-ionisation)
Remifentanil 0.17 - 0.33 hours 4 min 1.1 min

 

Action profile [RDM6:p401]

Action profile [RDM6:p401]
T1/2 alpha T1/2 beta T1/2 gamma Comment
Morphine 1 - 2.5 min 10 - 20 min 2 - 4 hours
Pethidine 5 - 15 min 3 - 5 hours

Fentanyl

1 - 2 min 10 - 30 min 2 - 4 hours
Sufentanil 1 - 2 min 15 - 20 min 2 - 3 hours

Alfentanil

1 - 3 min 4 - 17 min 1 - 2 hours
Remifentanil 0.5 - 1.5 min 5 - 8 min 0.7 - 1.2 hours

 

 

Physicochemical properties (lipid solubility, pKa and ionisation)

 

Physicochemical properties
Lipid solubility [SH4] Octanol/water partition coefficient [RDM6:p401] pKa % of non-ionised at pH 7.4 % of non-ionised at pH 7.4
Morphine 1 1.4 7.9 23%
Pethidine 32 39 8.5 7%
Fentanyl 955 813 8.4 8.5%
Sufentanil 1727 1778 8.0 20%
Alfentanil 129 145 6.5 89% Accounts for alfentanil's fast equilibration time
Remifentanil 17.9 7.3 58%

 

  • All opioids are weak base