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% ?)

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

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 [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

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%

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