PO/IV/IM/SC/SL/IT
Poor bioavailability 30% (good abs but high 1st pass metab)
onset / duration Oral ~30 minutes; I.V.: 5-10 minutes

IV/IM/TD. BA PO 30%SL50%skin>90%
onset IM.: 7-8 mins; IV imm; TD 6 hrs
duration IM:1-2 hrs; IV:0.5-1hr; TD 12hrs

relative lipid sol 1

but crosses BBB

pKa 8.0 (25% unionised)
slow redistribution

relative lipid sol 500

Rapid redistribution
pKa 8.4(10% union)

prot bind 20-40% (Alb)

prot bind 80-85%

mod Vd 3-4L/kg

Mod Vd 4-6L/kg

Metabolised to morphine-3-glucuronide (70%)
and morphine-6-glucuronide (10%) by gut wall and liver.
M6G is 10-20 times potent, may accumulate in renal failure

Slow Hepatic, primarily via CYP3A4clearance

Excreted mainly in urine as conjugates with 10% in faeces

excretion Urine 75%

Half time 2-4hrs (large interpatient Variability)

half life I.V.: 2-4 hours, prolonged context sensitive half time

CNS: dysphoria, confusion, ↓LoC, ↓cough reflex, miosis(PNS)
CVS: hypotension (↓TPR, blunt baroreceptor reflexes)
Resp: dir ↓resp drive indir via obtundation
GI: ↓gut motility, ↓SB secretions, CTZ→N+V, constipn, CBD spasm.
GU: Urinary retention
skin flushing, pruritis(histamine)
Dependence, addiction,Tolernce. IT – resp dep (rostral migration)

Similar to other opioids. Differences due to lipid sol.
Does not cause delayed respiratory depression because it rapidly diffuses into and out of the CSF. Raised CSHT prolonged infusion may lead to increased duration of action and SE