2010B01 Compare and contrast the pharmacokinetics of orally and intravenously
 administered morphine and oxycodone.

 

 

List:

·      Equipotent doses

·      Time course

·      Absorption

·      Distribution

·      Metabolism

·      Excretion

 

Equipotent doses:

 

Morphine

Oxycodone

IV

10mg

10mg

PO

30mg

20mg

 

Time course:

 

Morphine

Oxycodone

Onset (time to 80%) (mins)

10 mins

2-5mins

Peak effect (mins)

30 mins

? faster than morphine

Duration (hours)

3h

3h

 

Absorption:

 

Morphine

Oxycodone:

Oral bioav

30-50%

75%

 

Distribution:

 

Morphine

Oxycodone

Lipid solubility

1

1

pKa (weak bases)

8.0

8.5

% unionised at pH 7.4

23%

<10%

Active uptake into CNS

N

Y*

%Plasma protein bound

35%

45%

VDC (L/kg)

 

 

VDSS (L/kg)

3.5

2.5

t1/2ke0 (mins)

17

? faster

t1/2α (mins)

 

 

*Active uptake into CNS may account for oxycodone’s apparent faster onset despite similar size, lipid solubility and ionised fraction

 

Metabolism:

 

Morphine

Oxycodone

Organ

Liver

Liver

Mode

Phase 2(less affected in liver failure)

Phase 1 then 2

Clearance (mL/kg/min)

16

13

t1/2β (mins)

170

200

Metabolites

(1) Morphine-3-glucuronide (60%)

-Neurotoxic: seizures, confusion

-Inactive as analgesic

(2) Morphine-6-glucuronide (10%)

-Active: 14x analgesic potency

(3) Normorphine (30%)

-Inactive

(1) 3A4 -> noroxycodone (most)

(2) 2D6 -> oxymorphine (15%)

-14x analgesic potency

(3) 6α and 6β-oxycodol (10%)

(4) Oxycodone-n-oxide

 

Excretion:

 

Morphine

Oxycodone

Route

Metabolites -> urine*

Minimal morphine -> urine

Metabolites -> urine*

10% oxycodone -> urine

*Renal failure results in accumulation of active metabolites for both drugs, and oxycodone itself

 

 

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