Antiepileptics: gabapentin pharmacokinetics: practice question

A Pharmacology question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Pharmacology · Antiepileptics: gabapentin pharmacokinetics

Sample item

A 68-year-old man with diabetic neuropathic pain and an eGFR of 25 mL/min is given gabapentin 600 mg three times daily and becomes drowsy with myoclonus. What is the most likely explanation?

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

A. Accumulation because gabapentin is excreted unchanged by the kidney

Gabapentin, which binds the alpha-2-delta subunit of voltage-gated calcium channels, is not metabolised and is eliminated entirely by renal excretion. In reduced renal function it accumulates and causes sedation, dizziness and myoclonus, so doses must be reduced according to creatinine clearance.

Option by option

  • A. Accumulation because gabapentin is excreted unchanged by the kidney (correct)

    Reduced renal clearance leads directly to accumulation and toxicity.

  • B. Displacement from albumin by other drugs

    Gabapentin is hardly protein bound, so displacement does not occur.

  • C. Inhibition of its hepatic metabolism by diabetes

    Gabapentin undergoes no hepatic metabolism, so hepatic inhibition is irrelevant.

  • D. Conversion to a toxic active metabolite by CYP2D6

    Gabapentin has no active metabolite and no CYP2D6 pathway.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

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Questions about this Pharmacology question

What is the answer to this Pharmacology question?

The best answer is A, Accumulation because gabapentin is excreted unchanged by the kidney. Gabapentin, which binds the alpha-2-delta subunit of voltage-gated calcium channels, is not metabolised and is eliminated entirely by renal excretion.

Why is "Displacement from albumin by other drugs" not the answer?

Gabapentin is hardly protein bound, so displacement does not occur.

Why is "Inhibition of its hepatic metabolism by diabetes" not the answer?

Gabapentin undergoes no hepatic metabolism, so hepatic inhibition is irrelevant.

Why is "Conversion to a toxic active metabolite by CYP2D6" not the answer?

Gabapentin has no active metabolite and no CYP2D6 pathway.

What concept does this question test?

It tests Antiepileptics: gabapentin pharmacokinetics in Pharmacology. In reduced renal function it accumulates and causes sedation, dizziness and myoclonus, so doses must be reduced according to creatinine clearance.

How hard is this question?

We tag it as an application question: it asks you to use a fact on a patient or a finding. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Antiepileptics: gabapentin pharmacokinetics?

Learn drugs as classes, then the exception in each class that an examiner would pick. Then use the flashcards and the other Pharmacology questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.