1. DOSAGE ADJUSTMENT IN RENAL FAILURE
AND HEPATIC FAILURE
DEVSTHALI VIDYAPEETH COLLEGE OF PHARMACY
(Affiliated to Uttrakhand Technical University, Dehradun)
RUDRAPUR
PRESENTED TO:
MR. MANOJ BHARADWAJ
(ASSOCIATE PROFESSOR)
PRESENTED BY:
DEEPA JOSHI
B. PHARM
4TH YEAR
deepajoshi11.11dj@gmail.com

2. OVERVIEW
 Dose adjustment in Renal Failure
 Basics of kidney
 Common cause of kidney failure
 Dose adjustment based on drug clearance
 Identification of RENAL FUNCTION
• Criteria
• Inulin
• Creatinine
• Blood Urea Nitrogen
 Dose adjustment in Hepatic Failure
 Basic of liver
 Causes of hepatic failure
 Dosage adjustment in patient with hepatic impairment
 Liver Function Test
 Hepatic metabolism markers

3. BASICS OF KIDNEY
Kidney is the important organ for elimination of drug by mechanism of
GFR(Glomerulus filtration rate) & active tubular secretion & In normal case the
GFR rate is 120 ml/min.
Some chemical moieties is used for the identification of renal function.
Example: Inulin, Creatinine or some other marker.
RENAL FAILURE:
Renal failure or kidney failure describes a medical condition in which the kidney
fail to adequately filter toxins and waste products from the blood.
Renal failure is described as a decrease in glomerulus filtration rate(GFR).
Impairment of kidney function affects the pharmacokinetics of the drugs.
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4. CAUSES OF RENAL FAILURE
Condition Comment
Hypertension Chronic overloading of kidney with fluid and
electrolytes lead to kidney insufficiency.
Diabetes mellitus The disturbance of sugar metabolism may lead to
degenerative renal disease.
Nephrotoxic drugs Certain drugs like aminoglycosides,
Phenacetin cause irreversible kidney disease.
Hypovolemia Any condition that causes a reduction in renal
blood leads to renal damage.
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5. DOSE ADJUSTMENT BASED ON DRUG CLEARANCE
This method assume that the required therapeutic plasma drug concentration
in uremic patients is similar to that required in patients with normal renal
function.
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6. IDENTIFICATION OF RENAL FUNCTION:
For the identification of renal function we used following method:
1. Inulin
2. Creatinine
3. Blood Urea Nitrogen(BUN)
Inulin : Inulin is a fructose polysaccharide fulfil most of criteria listed for markers.
 Markers should be water soluble & non toxic.
 Not bind to cell or protein.
 Markers should be filtered through glomerulus filtration.
 Should not be metabolise.
Creatinine: The creatinine is an endogenous substance form from creatinine
phosphate by muscle metabolism.
Creatinine concentration in blood depends on many physiological factors like –
muscle mass, body weight, age.
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7. Blood Urea Nitrogen: The measurement of BUN is commonly used for diagnostic
test for the renal function.
The kidney failure increased the rate BUN, because urea is the end product of
metabolism of protein in body. The BUN level is 10-20mg/dl.
LIVER
Liver is the large glandular organ , involved in many metabolic processes.As it
does so, liver secretes bile that ends up back in the intestines.
LIVER FAILURE:
Liver failure is the inability of the liver to perform its normal synthetic and
metabolic function as part of normal physiology.
Causes of liver failure:
The liver can be damaged in a variety of ways:
 Cells can become inflamed (such as hepatitis).
 Bile flow can be obstructed(such as cholestasis).
 Cholesterol or triglycerides can accumulate (steatosis).
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8. DOSAGE ADJUSTMENT IN PATIENT WITH
HEPATIC IMPAIRMENT
Case 1: If the metabolism of drug is 20%.
Case 2: The drug is gaseous and voletile in nature because excretion of drug through
lungs.
Liver function tests and hepatic metabolic markers
Liver function :
 Synthesis and storage of amino acids, proteins, vitamins and fats.
 Blood glucose level
 Blood circulation and filtration.
Liver function test:
1. Amino transferase method
2. Alkaline phosphate method
3. Bilirubin
4. Prothrombin time
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9. HEPATIC METABOLIC MARKERS:
1.Aminotransferase method(AST) : AST value for males : 10-55U/L &
For females : 7-30 U/L.
2.Alkaline phosphatase(AT) : AP value for male : 45-115U/L &
For females : 30-100 U/L.
3.Bilirubin : Normal range : 0-1 mg/ml.
4.Prothrombin time: With the exception of factor 8, all coagulation factors are
synthesized by the liver, therefore hepatic disease can alter the coagulation.
Normal range is 11.2- 13.2 second.
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