Renal impariment

Renal impariment And dose Adjustment

1. Renal Impairment And Dose Adjustment GUIDED BY Dr. VAMSHI KRISHNA. T PRESENTED BY BAHUBALI N. PATIL 160617012 INDUSTRIAL PHARMACY

2. 2 CONTENTS Renal Impairment Common Causes of Kidney Failure Dosage Adjustment in Renal Impairment Glomerular Filtration Rate Serum Creatinine Concentration And Clearance Dosage Regimen in the Renal Impairment Conclusion References

3. Renal Impairment Chronic Kidney Disease (CKD) is worldwide public health problem affecting more then 50 million people, and more than 1 million of them are receiving kidney replacement therapy. Kidney is an important organ in regulating body fluids, electrolyte balance, removal of metabolic waste, and drug excretion from the body. Impairment or degeneration of kidney function affects the pharmacokinetics of drugs. 3

4. 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 flow leads to renal damage Common Causes of Kidney Failure 4

5. 5 Dosage Adjustment in Renal Impairment Dosage adjustment in patients with renal impairment is based on certain assumptions The concepts presented here can only be used if the following assumptions are valid for the particular patient. Steady-state conc n in the renally impaired patient and normal patient should be equal Drugs which are eliminated by renal are more affected in renal impairment then the drugs which are eliminated by non-renal In minor renal impairment dosage may not be adjusted unless the glomerular filtration rate falls below normal

6. 6 Measurement of Glomerular Filtration Rate Several drugs and endogenous substances have been used as markers to measure GFR These markers are carried to the kidney by the blood via the renal artery and are filtered at the glomerulus Therefore, the rate at which these drug markers are filtered from the blood into the urine per unit of time reflects the glomerular filtration rate of the kidney Changes in GFR reflect changes in kidney function

7. 7 Several criteria are necessary to use a drug to measure GFR: 1. The drug must be freely filtered at the glomerulus. 2. The drug must not be reabsorbed nor actively secreted by the renal tubules. 3. The drug should not be metabolized. 4. The drug should not bind significantly to plasma proteins. 5. The drug should not have an effect on the filtration rate nor alter renal function. 6. The drug should be nontoxic.

8. 8 Serum Creatinine Concentration And Creatinine Clearance Creatinine clearance may be defined as the volume of plasma cleared of creatinine per unit time. It can be calculated by the following formula: It is expressed in mL/min. Cl cr =  

9. 9 Cont ….. The clearance of creatinine is used most extensively as a measurement of GFR Creatinine is an endogenous substance formed from creatinine phosphate during muscle metabolism. Creatinine production varies with age, weight, gender of the individual. In humans creatinine is filtered mainly at the glomerulus, with no tubular re-absorption. It tends to be decrease in elderly patient.

10. 10 Calculation of creatinine clearance from serum creatinine concentration This method is used to estimate creatinine clearance from serum creatinine concentration. Adults This method considers both the age and the weight of the patient. For males For females, use 90% of the Cl cr value obtained in males.   Cl cr =

11. 11 To use the nomogram, connect the patient's weight on the second line from the left with the patient's age on the fourth line with a ruler. Note the point of intersection on R and keep the ruler there. Turn the right part of the ruler to the appropriate serum creatinine value and the left side will indicate the clearance in mL/min. Nomogram for evaluation of endogenous creatinine clearance

12. 12 Cont ….. Children There are a number of methods for calculation of creatinine clearance in children, based on the body length and serum creatinine concentration. Where Cl cr is given in mL/min/1.73 m 2 . The value 0.55 represents a factor used for children ages 1 to 12 years. Cl cr =  

13. 13 Nomogram for rapid evaluation of endogenous creatinine clearance ( Cl Cr ) in pediatric patients (aged 6–12 yr ). To predict Cl Cr , connect the child's S Cr (serum creatinine) and Ht (height) with a ruler and read the Cl Cr where the ruler intersects the center line.

14. 14 Classification of Renal Function Based on Estimated GFR ( eGFR ) or Estimated Creatinine Clearance ( Cl cr ) Stage Description b eGFR c (mL/min/1.72m 2 ) Cl cr d (mL/min) 1 Normal GFR ≥90 ≥90 2 Mild decrease in GFR 60-89 60-89 3 Moderate decrease in GFR 30-59 30-59 4 Severe decrease in GFR 15-29 15-29 5 End stage renal disease (ESRD) < 15 not on dialysis Requiring dialysis < 15 not on dialysis Requiring dialysis

15. 15 Dosage Regimen in the Renal Impairment Dosage regimen in normal patients is based on the size of maintenance dose, dosing interval and overall rate constant Dose   C   Dosing Interval C   Elimination Rate Constant C       =

16. 16 Dosage Regimen in the Renal Impairment Dosage regimen in order to meet patient’s need are done in 3 ways Adjust Dose, Maintain Same Dosing Interval     =

17. 17 Dosage Regimen in the Renal Impairment Dosage regimen in order to meet patient’s need are done in 3 ways Adjust Dose, Maintain Same Dosing Interval Adjust Dosing Interval, Maintain Same Dose     =

18. 18 Dosage Regimen in the Renal Impairment Dosage regimen in order to meet patient’s need are done in 3 ways Adjust Dose, Maintain Same Dosing Interval Adjust Dosing Interval, Maintain Same Dose Adjust Both, Dose and Dosing Interval     =

19. 19 Dose Adjustment in Renal impairment by Determining Renal Function Renal Function (RF)   = Dosage Regimen need not be changed when The fraction of drug excreted unchanged is ≤ 0.3 The renal function RF is ≥ 0.7 of normal

20. 20 Dose Adjustment in Renal impairment by Determining Renal Function The required dose in patient with renal impairment can be calculated by the simple formula: Drug dose in renal impairment = Normal dose x RF The dosing interval in hrs can be computed from the following eqution : Dosing interval =  

21. 21 Conclusion The kidneys are important for the body’s ability to excrete medication. Diseases of the kidneys, in addition to ageing often require doses to be lowered in order to avoid adverse drug reactions. Moderately impaired kidney function may require lower medication doses and dosage regimen.

22. 22 References Leon Shargel , Susanna Wu-Pong, Andrew Yu; Applied Biopharmaceutics & Pharmacokinetics; 6 th edition; Page No 617-627 PL Madan; Biopharmaceutics & Pharmacokinetics; 2 th edition; Page No 405-425 D. M. Brahmankar , Sunil B. Jaiswal; Biopharmaceutics & Pharmacokinetics – A Treatise; 3 th edition; Page No 211-213

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