Step 1: Decide what kind of interaction this is:
The patient was stable on lithium, so the lithium dose did not change. Only one new drug was added, and the blood level of lithium went up. That points to a pharmacokinetic interaction, where the new drug changes how the body gets rid of lithium.
We then ask which of absorption, distribution, metabolism or excretion is involved. For lithium, only excretion matters.
Step 2: Why only excretion matters for lithium:
Lithium is a small ion. The liver does not break it down and it does not bind to plasma proteins. So liver enzyme changes and protein binding displacement cannot raise its level.
Kidney handling decides the level. A fall in GFR or a rise in proximal tubular sodium reabsorption leads to higher lithium.
Step 3: Find what the COX inhibitor does at the kidney:
Renal prostaglandins keep the afferent arterioles open. When COX is blocked, the afferent arterioles constrict and renal blood flow drops.
GFR falls, so less lithium is filtered. Sodium and lithium reabsorption in the proximal tubule also rises. Lithium clearance falls enough in some patients to cause toxicity.
Step 4: Eliminate by mechanism:
Option (A) talks about RBC glutathione. That is a hemolysis mechanism and has nothing to do with lithium excretion.
Option (C) says hepatic microsomal enzymes are inhibited. Lithium does not go through liver metabolism, so this cannot explain the rise.
Option (D) says tubular secretion increases. More secretion means a lower level and less toxicity. The case shows the opposite.
Step 5: Pick the mechanism that fits:
Option (B) states that renal prostaglandin synthesis is inhibited, GFR falls and lithium clearance falls. It explains why lithium rises and why symptoms appear.
Step 6: Practical point:
If an NSAID cannot be avoided in a patient on lithium, the lithium level should be checked within about a week and the dose lowered if needed. Aspirin and sulindac affect lithium the least.
Final Answer:
Lithium depends on the kidney for clearance. COX inhibitors reduce renal prostaglandins, lower GFR and lower lithium clearance. The answer is option (B).