| Drug | pKa | Oral bioavailability (%) | Lipophilicity | Protein binding (%) | Volume of distribution | Metabolic enzymes | Active metabolites | Excreted unchanged in urine (%) | Half-life |
|---|---|---|---|---|---|---|---|---|---|
Morphine | 7.9 | 15–64 | + | 30 | 3–5 L/kg | UGT2B7 | M6G (A) M3G (CNS+) | 10 | 1.7–3 hours |
Codeine | 8.2 | 60–90 | + | 20 | 3–4 L/kg | UGT2B7 CYP2D6 | Morphine (A) | 0 | 2–4 hours |
Diamorphine | 7.6 | – | ++ | – | 70 L | Esterases | Morphine (A) | Minimal | 2–3 minutes |
Hydromorphone | 8.2 | 50 | + | <10 | 295 L | UGT2B7 UGT1A3 | H3G (I) H6G (A) | 6 | 2–3 hours |
Tramadol | 9.4 | 70–90 | + | 20 | 2.6–2.9 L/kg | CYP3A4 CYP2D6 | M1 | 90 | 6 hours |
Buprenorphine | 8.4 | 15 | +++ | 96 | 430 L | CYP3A4 UGT1A1/1A3 | – | Minimal | *Complicated by enterohepatic recirculation |
Meperidine (pethidine) | 8.5 | – | ++ | 60–80 | 3–5 L/kg | CYP3A4 CYP2B6 CYP2C19 | Norpethidine (A, CNS+) | 5 | 3–6 hours |
Oxycodone | 8.5 | 60–87 | + | 45 | 2–3 L/kg | CYP3A4 CYP2D6 | Oxymorphone (A) | < 10 | 3–4 hours |
Methadone | 8.3 | 60–90 | ++ | 60–90 | 3–6 L/kg | CYP3A4 CYP2B6 (CYP2D6,2C9,2C19,1A2) | – | 15–60 | 15–20 hours (13–47) |
Fentanyl | 8.4 | – | +++ | 90 | 3–8 L/kg | CYP3A4 | – | < 7 | 2–7 hours |
Alfentanil | 6.5 | – | ++ | 90 | 0.4–1 L/kg | CYP3A4 | – | Minimal | 1–2 hours |
| Drug | pKa | Oral bioavailability (%) | Lipophilicity | Protein binding (%) | Volume of distribution | Metabolic enzymes | Active metabolites | Excreted unchanged in urine (%) | Half-life |
|---|---|---|---|---|---|---|---|---|---|
Morphine | 7.9 | 15–64 | + | 30 | 3–5 L/kg | UGT2B7 | M6G (A) M3G (CNS+) | 10 | 1.7–3 hours |
Codeine | 8.2 | 60–90 | + | 20 | 3–4 L/kg | UGT2B7 CYP2D6 | Morphine (A) | 0 | 2–4 hours |
Diamorphine | 7.6 | – | ++ | – | 70 L | Esterases | Morphine (A) | Minimal | 2–3 minutes |
Hydromorphone | 8.2 | 50 | + | <10 | 295 L | UGT2B7 UGT1A3 | H3G (I) H6G (A) | 6 | 2–3 hours |
Tramadol | 9.4 | 70–90 | + | 20 | 2.6–2.9 L/kg | CYP3A4 CYP2D6 | M1 | 90 | 6 hours |
Buprenorphine | 8.4 | 15 | +++ | 96 | 430 L | CYP3A4 UGT1A1/1A3 | – | Minimal | *Complicated by enterohepatic recirculation |
Meperidine (pethidine) | 8.5 | – | ++ | 60–80 | 3–5 L/kg | CYP3A4 CYP2B6 CYP2C19 | Norpethidine (A, CNS+) | 5 | 3–6 hours |
Oxycodone | 8.5 | 60–87 | + | 45 | 2–3 L/kg | CYP3A4 CYP2D6 | Oxymorphone (A) | < 10 | 3–4 hours |
Methadone | 8.3 | 60–90 | ++ | 60–90 | 3–6 L/kg | CYP3A4 CYP2B6 (CYP2D6,2C9,2C19,1A2) | – | 15–60 | 15–20 hours (13–47) |
Fentanyl | 8.4 | – | +++ | 90 | 3–8 L/kg | CYP3A4 | – | < 7 | 2–7 hours |
Alfentanil | 6.5 | – | ++ | 90 | 0.4–1 L/kg | CYP3A4 | – | Minimal | 1–2 hours |
Enzymes: CYP, cytochrome P450, UGT, UDP-glucuronosyltransferase. Metabolites: M3G, morphine-3-glucuronide, M6G, morphine-6-glucuronide H3G, Hydromorphone-3-glucuronide, H6G, Hydromorphone-6-glucuronide, M1, O-desmethyl tramadol. Active metabolites: A, analgesically active, CNS+, CNS excitability.
