MDG5204 Chap.4 Renal Excretion and Dose Adjustment
Renal Excretion and Dose Adjustment
The last pharmacokinetic process
Excretion is the irreversible physical removal of a drug and its metabolites from the body. Drugs leave through the kidneys, the intestine and bile, the lungs for gases and volatile liquids, and breast milk, which matters for a breastfed infant. The kidney is the main route and handles all water-soluble substances, which is why its function largely decides how long many drugs act.
Because excretory organs other than the lungs clear polar compounds far better than lipid-soluble ones, excretion depends on the metabolism described in the previous chapter.
Filtration, reabsorption and secretion
What appears in urine is what was filtered at the glomerulus, minus what was reabsorbed along the tubule, plus what was actively secreted into it.
Only unbound drug is filtered, and the glomerular filtration rate, normally about 120 mL/min, measures the volume of plasma filtered per unit time. Most of the filtrate returns to the blood, and lipid-soluble, unionised drug returns with it.
Tubular secretion is an active, carrier-mediated process with separate systems for anions and cations, and because the carriers are non-specific, drugs compete for them.
Turning physiology into treatment
Two clinical tools come from those processes.
Ion trapping uses urinary pH: a weak acid is ionised in alkaline urine, cannot diffuse back and is excreted, which is why alkalinising the urine is used in barbiturate and salicylate poisoning.
Carrier competition is used deliberately when probenecid is given with penicillin, reducing penicillin secretion so that its level stays higher for longer.
Estimating function and adjusting the dose
Renal excretion falls with reduced renal blood flow, as in heart failure, haemorrhage and shock, with renal disease, with NSAIDs that reduce renal perfusion, and at the extremes of age.
Creatinine clearance estimates the glomerular filtration rate, and the Cockcroft-Gault equation estimates it from age, weight and serum creatinine.
The course sets the threshold for adjusting renally excreted drugs at a creatinine clearance below 60 mL/min, with minor adjustment between 30 and 60 and major adjustment below 15, and gives two strategies: keep the dose and lengthen the interval, as for gentamicin, or keep the interval and lower the dose, as for digoxin.
What this chapter covers
- 01
Excretion routes and why the kidney dominates
- 02
Glomerular filtration of free drug and the normal filtration rate
- 03
Tubular reabsorption of unionised, lipid-soluble drug
- 04
Ion trapping and the use of urinary pH in poisoning
- 05
Active tubular secretion and probenecid competition with penicillin
- 06
Creatinine clearance thresholds and the two dose-adjustment strategies
Worked example · free
Deciding whether urinary alkalinisation will help
- 2State what alkaline urine does to a weak acid.
- 1Explain why that increases excretion.
- 2State why the course does not use urinary acidification.
Key terms
- Glomerular Filtration Rate
- The volume of plasma the glomeruli filter each minute, normally about 120 mL/min.
- Tubular Secretion
- Active, carrier-mediated transfer of drug from peritubular capillaries into the tubular lumen.
- Ion Trapping
- Retention of an ionised weak acid or base in a compartment whose pH prevents it diffusing back.
- Creatinine Clearance
- The volume of plasma cleared of creatinine per unit time, used to estimate glomerular filtration.
Renal Excretion and Dose Adjustment FAQ
Why does protein binding reduce renal filtration of a drug?
The glomerulus filters plasma water and small solutes, and a drug bound to albumin is carried as part of a large protein that is not filtered. Only the unbound fraction passes into the tubule, so extensive binding slows renal elimination unless the drug is also actively secreted.
When does a renally cleared drug need a dose change?
The course sets the trigger at a creatinine clearance below 60 mL/min. Between 30 and 60 a minor adjustment is made, below 15 a major one, and for drugs with a narrow therapeutic index blood levels are also measured. Drugs cleared mainly in bile, such as ceftriaxone, are the exception.
Why would a doctor give probenecid alongside penicillin?
Both are organic anions secreted by the same carrier in the proximal tubule. Probenecid has a high affinity for it and competes penicillin off, so less penicillin is secreted, its excretion slows and its plasma level stays higher for longer, prolonging its action without a larger dose.
Exam move
Draw the nephron once and label where filtration, reabsorption and secretion act, then attach each clinical example to its place on the drawing. Practise one Cockcroft-Gault estimate and one dose-adjustment decision until the thresholds come without looking.
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