Renal

Question 1

Assessment of kidney function

Answer 1

Measured GFR is the gold standard

Measured ClCr based on measured urinary clearance

Estimated ClCr or eGFR based on SeCr widely used clinically

Question 2

Limitations

Answer 2

SeCr is generated from muscle mass and diet

Tubular secretion of SeCr

Must be stable because not changing a lot

only small changes

Question 3

CKD

Answer 3

kidney damage

urine albumin-creatinine ratio > 30 mg/g

GFR < 60 mL/min for >3 months

Whys is the important?
age-related reductions in renal function
CKD mediations
concomitant disorders

Question 4

CKD ADME

Answer 4

absorption: inconsistent

distribution: changes in volume of distribution
alterations in protein or tissue binding
alterations in fluid volume

metabolism: changes in non-renal clearance

excretion: reduced renal clearance

Question 5

CKD PK changes

Answer 5

reduced bioavailability due to gut wall edema

reduced due to drug interactions

reduced due to changes increased gastric pH

Question 6

Changes in bioavailability

Answer 6

alterations in intestinal or hepatic drug metabolism
alterations in uptake or efflux transporters

increased bioavailability of CYP3A, CYP2D6

Question 7

Drug distribution

Answer 7

Alterations in plasma volume:
fluctuations in volume, and increased fluid administration

Hydrophilic drugs: aminoglycosides

Alterations in plasma protein binding:
-decreased binding of many acidic drugs to albumin

Decreased tissue binding

Question 8

Metabolism and transport

Answer 8

complex and prediction of the impact of a given drug on metabolism and/or drug transporters is difficult

no quantitative strategy for making predictions even within the same class

qualitative strategies for may be employed by knowing the enzyme or transporter involved