|
|
Morphine |
Codeine |
Pethidine |
|
Location |
Liver |
Liver |
Liver |
|
Pathway + metabolites |
Liver Phase 1: -N-demethylation (3A4) -> normorphine (5%) -Methylation (?) -> codeine (few %) Phase 2: -Glucuronidation -> M6G (10%) (Analgesia 15x morphine, resp depression) -Glucuronidation -> M3G (70%) Neurotox: confusion, seizures |
Liver Phase 1: -N-demethylation (3A4) -> norcodeine (15%) -O-demethylation (2D6) -> morphine (10%) (analgesia 10x codeine) i.e. metabolism needed for effect Phase 2: -Glucuronidation -> C6G Weak analgesia |
Liver Phase 1: -N-demethylation (2B6, 2C19, 3A4)-> Norpethidine (90%) Analgesia 0.5x pethidine Seizures Long t1/2β 12-24 hours -Ester hydrolysis -> pethidinic acid |
|
Excretion |
Minimal morphine -> urine 100% metabolites -> urine |
? Metabolites -> urine |
1-25% pethidine -> urine 100% metabolites -> urine |
|
Clearance (mL/kg/min) |
16 |
? |
12 |
|
t1/2β (mins) |
170 |
? 120 |
Parent: 210 Norpethidine: 12-24 hours |
|
Oral bioav |
33-50% |
60% |
50% |
|
Induction, inhibition |
|
2D6 non-inducible |
Yes |
|
Polymorphism |
Minimal |
2D6 polymorphism common ↓↓Active 10% Caucasians, 30% East Asians (no analgesia) ↑↑Active ?30% North Africans (↑↑risk sedation, resp depression) |
Minimal |
|
Liver failure |
Minimal effect |
↓analgesia |
? |
|
Kidney failure |
Metabolites accumulate |
Metabolites accumulate |
Metabolites accumulate |
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