Pharmacokinetics of Statin drugs Pravastatin and Rosuvastatin

1. Hyperlipidemia
FRETZ D. ALFARO
JHONNY
PHARMACY 3F

2. Introduction
 Hyperlipidemia means
abnormally increased
cholesterol level, one of
the risk factors for
atherosclerosis
(deposition of fats at
walls of arteries,
forming plaque)
Risk factors
 Cigarette smoking
 Diabetes
 Obesity
 Hypertension
 oxidative stress

3. Factors that lead to
to Hyperlipidemia
Ways to prevent
Hyperlipidemia
 Unhealthy diet
 Physical Inactivity
 Smoking
 Drinking Alcohol
 Family history of
heart disease
 Dietary Management
 Exercise
 Quit smoking
 Quit drinking
alcoholic beverages
 Visit a doctor

4. Anti-hyperlipidemic drugs are mainly
classified into five types they are:

5. MECHANISM OF ACTION
STATINS

6. Mechanism of Action
Inhibiting rate limiting enzyme of
cholesterol synthesis
Ex. HMG-CoA reductases
• Effects on lipids:
• Decrease bad cholesterol
• Decrease very low density lipoprotein
• Decrease triglycerides
• Increase good cholesterol

7. HMG - CoA
Mevalonate
Farnesyl
Pyrophosphate
Squaline
Cholesterol
Acetoacyl CoA
HMG CoA
Syntase
HMG CoA
Reductase

8. PHARMACOKINETICS

9. PRAVASTATIN ROSUVASTATIN
 Absorption
 Peak plasma concentration
were reached 1 to 1.5 hours
after administration.
 Absolute bioavailability =
17%
 Food decreases the
systemic bioavailability but
the lipid-lowering effect is
not impacted.
 Absorption
 Peak plasma concentrations
were reached 3 to 5 hours
following oral dosing.
 Absolute bioavailability =
20%.
 Food did not affect the AUC
of rosuvastatin.

10. PRAVASTATIN ROSUVASTATIN
 Volume of distribution
Not Available
 Protein binding
50% bound to human
plasma proteins.
 Half-life
The elimination half-life =
1.5 to 2 hours.
 Distribution
Volume of distribution at
steady-state of rosuvastatin
is approximately 134 liters.
 Protein binding
88% bound to plasma
proteins, mostly albumin.
 Half-life
The elimination half-life =
19 hours

11. PRAVASTATIN ROSUVASTATIN
Metabolism
Undergoes extensive
first-pass metabolism in
the liver, its primary site
of action.
Metabolism
 Rosuvastatin is not
extensively metabolized

12. PRAVASTATIN ROSUVASTATIN
Excretion
Oral
 70% = Feces
 20% = Urine
 IV
 47%= Renal excretion
 53%= Hepatic excretion
Excretion
Oral
 90%= Feces
IV
 28% = Renal excretion
 72% = Hepatic excretion

13. COMPARISON ON EFFECTS
Medication Dose LDL TG HDL
Reduction Reduction Increase
Rosuvastatin 10-40 mg 40-70% 20-30% 5-
15%
Pravastatin 10-40mg 19-40% 10-25% 3-
10%

14. Drug Interactions
PRAVASTATIN ROSUVASTATIN
Cholestyramine/Colestipol:
 Decreases the AUC of
Pravastatin by 40-50%
Fibrates (eg, gemfibrozil):
 Associated with
myopathy
Colchicine:
 Cases of myopathy,
including rhabdomyolysis
Antacids:
 Decreases plasma
concentration by 50%

15. END