Absorption and distribution

Question 1

1
describe prednisolone

Answer 1

is a synthetic glucocorticoid used for its anti-inflammatory and immunosuppressive effects.

Question 2

describe prednisolone
mechanism of absorption
bioavailability
peak plasma concentration
half-life
factors affecting absorption
elderly patients I see

Answer 2

Prednisolone is a synthetic glucocorticoid used for its anti-inflammatory and immunosuppressive effects.
After oral intake Prednisolone is absorbed in the small intestine specifically the proximal duodenum. Due to its rapid absorption it becomes almost completely (80%-100%) available.
Oral administration of prednisolone is commonly used within my practice. IV prednisolone reaches systemic circulation directly whereas IM prednisolone absorption is slow and occurs via the lymphatic system.
Prednisolone’s small lipophilic nature allows it to be absorbed rapidily in the intestininal lumen, where it passively diffuses through the phospholipid bilayer into the bloodstream. Also driven by the high drug concentration gradient in the the GI lumen to the low concentration gradient in the bloodstream. This process does not require ATP or specific transporters. The oral formulation has 70% bioavailability that goes into the systemic circulation, the first fass-effect through the liver does not affect the bioavailability of prednisolone. Peak plasma concentration occurs within 1-3 hours. The half-life of prednisolone is 3 hours and is longer in old age and with people with liver disease due to lower albumin levels.
Factors which affect absorption rate include
1. older age can affect the:
2. Stomach emptying rate
3. Gastric pH, mucus and bile
4. Gastric motility
5. Blood flow to the absorption site (e.g. septic shock reduces blood flow).
6. Food composition as fatty foods slow gastric emptying and motility

Distribution:
65-91% of prednisolone is protein-bound
Prednisolone binds to corticosteroid-binding globulin (CBG): transcortin and Albumin with the remaining drug active.
CBG acts as both a transporter and a reservoir, shuttling the drug through the bloodstream to be widely distributed to tissues and cells.
While bound to CBG or albumin, prednisolone is inactive because it is too large to cross cell membranes.
only the free form of prednisolone is active and can cross cell membranes to bind to glucocorticoid receptors in target cells such as in the lungs.
Increased weight and fat increases the volume of distribution for highly lipophilic drugs like prednisolone resulting in delayed maximal effect, and the opptite for underweight patients.
Prednisolone can cross the blood brain barrier through passive diffusion and can basically reach all brain cells and binds to GR to exert its effect. 88% of prednisolone is inactivated as it crosses the placenta and small amounts pass into breast milk. Extra monitoring of mother and foetus growth may be required.

Question 3

Factors affecting absorption

Answer 3

1. Stomach emptying rate
2. Gastric pH, mucus and bile
3. Gastric motility
4. Blood flow to the absorption site (e.g. septic shock reduces blood flow).
5. Food composition as fatty foods slow gastric emptying and motility

Question 4

Distribution

Answer 4

65-91% of prednisolone is protein-bound
Prednisolone binds to corticosteroid-binding globulin (CBG): transcortin and Albumin with the remaining drug active.
CBG acts as both a transporter and a reservoir, shuttling the drug through the bloodstream to be widely distributed to tissues and cells.
While bound to CBG or albumin, prednisolone is inactive because it is too large to cross cell membranes.
only the free form of prednisolone is active and can cross cell membranes to bind to glucocorticoid receptors in target cells such as in the lungs.
Prednisolone can cross the blood brain barrier through passive diffusion and can basically reach all brain cells and binds to GR to exert its effect. 88% of prednisolone is inactivated as it crosses the placenta and small amounts pass into breast milk. Extra monitoring of mother and foetus growth may be required.

Question 5

VD

Answer 5

Volume of Distribution (VD) is moderate, allowing it to penetrate tissues effectively.
0.15 mg/kg dose: VD = 29.3 L
0.30 mg/kg dose: VD = 44.2 L