Renal variability

1. Free fraction of drug is filtered in blood

2. Active transporters pull drug from blood stream and into renal tubule (OAT, OCT, etc)

3. Metabolism by Kidney

4. Reabsorption by active transport (some of it)

5. Ionized fraction is trapped in urine by pH (some of it)

6. most is excreted in urine

Steps of Renal excretion

• Volume of Distribution

• Protein Binding

• Lipid Solubility/polarity (more polar the drug, the more its excreted)

• Renal blood flow

• Disease state

• Age

Major determinants of Glomerular filtration

• Competitive inhibition

• Concentration

• Protein binding

• Renal blood flow

• Genetic Polymorphism

Major determinants of Tubular Secretion

• Beta lactams

• Frusemide

• HCTZ

• Probenecid

These drugs inhibit OAT and prevent excretion of drugs from the kidney (prevent OAT from pulling drugs into kidney tubule)

• Procainamide

• Cimetidine/ranitidine

• Trimethoprim

• Ethambutol

These drugs Inhibit OCT and prevent excretion of drugs from the kidney (prevent OCT from pulling drugs into kidney tubule)

• Zidovudine

• Ribavirin

• Gemcitabine

These drugs Inhibit Nucleoside transporters and prevent secretion 

• Digoxin

• Verapamil

• Cyclosporin 

These drugs affect and inhibit PgP efflux in regard to tubular secretion

• Urine flow rate

• Urine pH

• Active transport 

Major determinants of Reabsorption

More excreted; in the charged form

When a drug is polar it is ______ and is trapped in urine when it is _____

Kidney damage with normal or increased GFR

GFR > 90 indicates

1. Assess renal function

   1. Measure SCr

   2. Estimate CrCL

   3. Calculate CrCL

2. Estimate PK consequences

3. Adjust dose

When dosing adjustments need to be made in CKD

• Loading doses

When dosing adjustments DO NOT need to be made in CKD

1. Dose reduction (smallest peak -troughs)

2. Lengthening dose interval (Largest peak troughs)

3. or BOTH

What dose adjustments CAN WE DO in CKD patients?