A Textbook of Clinical Pharmacology and Therapeutics

●Introduction 31

●Glomerular filtration 31

●Proximal tubular secretion 31

●Passive distal tubular reabsorption 32

●Active tubular reabsorption 33

CHAPTER 6

RENAL EXCRETION OF DRUGS

INTRODUCTION

The kidneys are involved in the elimination of virtually every
drug or drug metabolite (Figure 6.1). The contribution of renal
excretion to total body clearance of any particular drug is

determined by its lipid solubility (and hence its polarity).

Elimination of non-polar drugs depends on metabolism

(Chapter 5) to more polar metabolites, which are then excreted

in the urine. Polar substances are eliminated efficiently by the

kidneys, because they are not freely diffusible across the tubu-

lar membrane and so remain in the urine, even though there is

a concentration gradient favouring reabsorption from tubular

to interstitial fluid. Renal elimination is influenced by several

processes that alter the drug concentration in tubular fluid.

Depending on which of these predominates, the renal clear-

ance of a drug may be either an important or a trivial compo-

nent in its overall elimination.

GLOMERULAR FILTRATION

Glomerular filtrate contains concentrations of low-molecular-

weight solutes similar to plasma. In contrast, molecules with a

molecular weight of 66 000 (including plasma proteins and

drug–protein complexes) do not pass through the glomerulus.

Accordingly, only free drug passes into the filtrate. Renal

impairment (Chapter 7) predictably reduces the elimination of

drugs that depend on glomerular filtration for their clearance

(e.g.digoxin). Drugs that are highly bound to albumin or α-1

acid glycoprotein in plasma are not efficiently filtered.

PROXIMAL TUBULAR SECRETION

There are independent mechanisms for active secretion of

organic anions and organic cations (OAT and OCT) into the

proximal tubule. These are relatively non-specific in their

structural requirements, and share some of the characteristics

of transport systems in the intestine. OAT excretes drugs, such

asprobenecidandpenicillin. Para-aminohippuric acid (PAH)

is excreted so efficiently that it is completely extracted from

Free drug enters

glomerular filtrate

Active secretion

Can be affected by other

drugs: main site for

interactions in the

kidney

Passive reabsorption

of lipid-soluble,

unionized drug

Ionized, lipid-insoluble drug

into urine

Collecting duct

Distal tubule

Loop of Henle

Proximal tubule

1

2

3

Figure 6.1:Urinary elimination of drugs and metabolites by
glomerular filtration and/or tubular secretion and reabsorption.