Lecture 11 RENAL CLEARANCE Excretion 80 Urine Kidneys

Lecture #11 RENAL CLEARANCE

Excretion • 80% Urine (Kidneys) • 20% Bile

Renal Blood Flow (QR) Heart Kidney Renal Artery Renal Vein Vena Cava Excreted Ureter Bladder Aorta

Kidneys Kidney Ureter Aorta Vena Cava Liver Kidney Ureter Bladder

Nephron Kidney Renal Artery Bowman’s capsule tery Renal Vein Ureter

Glomerulus (Filtration) filtration slit pedicel pored glomerular cells basal lamina (X larger proteins) filtration slit podocyte

Tubules (Secretion and Reabsorption) Side View Nephron Urine Blood Plasma Drug Transporters Cross-Section Urine Kidney Proximal Convoluted Tubule

Factors that Influence Renal Clearance Renal Artery Filtration Secretion Renal Vein Reabsorption Excretion (Urine) Ureter

Rate of Excretion

Renal Clearance (CLR) Clearance by Filtration (called the glomerular filtration rate) Confusing Book Point: GFR is equivalent to CLf Clearance by Secretion

Glomerular Filtration Rate fraction unbound [Drug]plasma

Flow Rate Approximations

Urinary Flow Rate is Highly Variable Urine Flow Rate (UFR) Average = 68 ml/hr Our approximation UFR = 1 ml/hr/kg or 70 ml/hr

Renal Extraction Ratio (ER) Confusing Book Point: They use extraction rate and excretion rate the same.

Renal Extraction Ratios (ER)

Contributions of filtration and secretion

Urine, CLR and ER Reabsorption Filtration Secretion Concentration of Drug in the Urine Flow Rate

Factors that Influence (CLR) • • p. H Altered Secretion Renal Impairment Protein Binding

Factors that Influence Passive Diffusion: p. H partition hypothesis

plant hormone/antipyretic p. Ka=2. 97

Urine Acidification and Alkalinization in the Treatment of Drug Overdose • Drug is a weak acid – Urine alkalinization (Increase p. H) • IV sodium bicarbonate – Phenobarbital, Aspirin or Salicylates – Herbicide 2, 4 -dichlorophenoxyacetic acid poisoning • Drug is a weak base – Urine acidification (Decrease p. H) • IV ammonium chloride – Amphetamines (metabolic acidosis)

Altered Active Tubular Secretion CLR =24 L/hr to 14 L/hr Inhibit Tubular Secretion

Low ER (Renal Impairment) Anti-seizure

Altered Protein Binding *Clofibric acid is a metabolite of the cholesterol-lowering pharmaceutical drug clofibrate.

Renal Metabolism (Minor) kidney UDP-glucuronosyltransferase (UDPG) Activity Pharmacological Reviews March 1, 1998 vol. 50 no. 1 107 -142