Dose Adjustment in Renal Diseases
Dose Adjustments in Patients with Impaired Renal Function
Prof. Hartmut Derendorf
University of Florida
Chronic Kidney Disease
Major world-wide health concern In US number of patients requiring dialysis or transplant is projected to increase from 340,000 in 1999 to 651,000 in 2010 National Kidney Foundation-attempts to standardize definition, stages and laboratory tests to assess kidney function
Am J Kidney Dis. (2000) 366 suppl 2:S1–S279 S-M Huang et al. Clinical Pharmacology & Therapeutics (2009) 86 5, 475–479
Chronic Kidney Disease - Definition
“Kidney damage for three months or more, with or without decreased GFR, manifested by pathologic abnormalities or markers of kidney damage, including abnormalities in the composition of the blood or urine or abnormalities in imaging tests” GFR < 60 mL per minute per 1.73 m2 for three months or more, with or without kidney damage
National Kidney Foundation, 2004
Renal Drug Clearance
• Glomerular Filtration • Tubular Secretion • Tubular Re-absorption
- 20-25% Cardiac output or 1.1L/min goes to kidneys - 10% of it is filtered at glomerulus - Normal GFR is 120 ml/min for a 70kg, 20 year old man
Verbeeck RK, et al. Eur J Clin Pharmacol (2009) 65:757–773
Effect of Renal Dysfunction on PK processes
• Absorption
- increased tmax for certain drugs in severe renal dysfunction - Changes pre-systemic elimination
• Distribution
- Plasma protein binding of many acidic drugs decrease in renal impairment - 1-Acid glycoprotein levels may show an increase - Changes in volume of distribution
• Metabolism
- Renal dysfunction may alter even non-renal elimination - Accumulation of active metabolites
• Elimination
- Transporters - Renal failure may affect multiple organ systems
Dose adjustments!
Estimation of Renal Function
GFR as overall measure of renal function Exogenous markers like inulin – not widely used clinically Most popular- Creatinine clearance from serum creatinine
Prof. Hartmut Derendorf
University of Florida
Chronic Kidney Disease
Major world-wide health concern In US number of patients requiring dialysis or transplant is projected to increase from 340,000 in 1999 to 651,000 in 2010 National Kidney Foundation-attempts to standardize definition, stages and laboratory tests to assess kidney function
Am J Kidney Dis. (2000) 366 suppl 2:S1–S279 S-M Huang et al. Clinical Pharmacology & Therapeutics (2009) 86 5, 475–479
Chronic Kidney Disease - Definition
“Kidney damage for three months or more, with or without decreased GFR, manifested by pathologic abnormalities or markers of kidney damage, including abnormalities in the composition of the blood or urine or abnormalities in imaging tests” GFR < 60 mL per minute per 1.73 m2 for three months or more, with or without kidney damage
National Kidney Foundation, 2004
Renal Drug Clearance
• Glomerular Filtration • Tubular Secretion • Tubular Re-absorption
- 20-25% Cardiac output or 1.1L/min goes to kidneys - 10% of it is filtered at glomerulus - Normal GFR is 120 ml/min for a 70kg, 20 year old man
Verbeeck RK, et al. Eur J Clin Pharmacol (2009) 65:757–773
Effect of Renal Dysfunction on PK processes
• Absorption
- increased tmax for certain drugs in severe renal dysfunction - Changes pre-systemic elimination
• Distribution
- Plasma protein binding of many acidic drugs decrease in renal impairment - 1-Acid glycoprotein levels may show an increase - Changes in volume of distribution
• Metabolism
- Renal dysfunction may alter even non-renal elimination - Accumulation of active metabolites
• Elimination
- Transporters - Renal failure may affect multiple organ systems
Dose adjustments!
Estimation of Renal Function
GFR as overall measure of renal function Exogenous markers like inulin – not widely used clinically Most popular- Creatinine clearance from serum creatinine