131 / 795
3. 
3.1.3.5.3.2. Pharmacokinetics of opioids Pharmacokinetics
[SH4:p87-p90,p93-p102]
Distribution (Vd and protein binding)
| 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)
| 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)
| 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]
| 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)
| 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