Older PPARα agonist — similar TG/HDL profile to fenofibrate. Problematic CYP2C8 inhibition → raises statin levels → substantial rhabdomyolysis signal. Fenofibrate preferred in statin combinations for this reason.
Half-Life (t½)
PO: 1.5h
Dosing Guidelines
PO: Typical 600 mg (Range: 600–600 mg)
Target Organ Systems
cardiovascular
digestive
Interactions
Simvastatin / statins (major): Gemfibrozil glucuronide is a mechanism-based CYP2C8 inactivator (Ogilvie 2006: K_I 20–52 µM, k_inact 0.21/min in HLM). Solver approximates as competitive Ki = 35 µM (midpoint); time-dependent inactivation accumulates over repeated dosing, so real clinical AUC effect is larger than this static approximation. FDA explicitly warns against this combination — use is contraindicated.
Repaglinide (contraindicated): CYP2C8 mechanism-based inhibition. Niemi 2003 (PMID:12687332): gemfibrozil raised repaglinide AUC 8.1× (range 5.5-15×) and prolonged t½ 1.3→3.7 h. Dose-response confirmed at 30-900 mg gemfibrozil (Honkalammi 2011). Combination contraindicated due to severe hypoglycemia risk.
Cerivastatin (major): CYP2C8 inhibition. Backman 2002 (PMID:12496749) verbatim: "the area under the plasma concentration-time curve [AUC(0-infinity)] of parent cerivastatin was on average 559% (range, 138% to 995%; P =.0002) ... of the corresponding values in the placebo phase". 10 healthy volunteers, randomized double-blind crossover, gemfibrozil 600 mg bid × 3d + single 0.3 mg PO cerivastatin. AUC ratio 5.59×; Ki ≈ 35/4.59 = 7.62 µM. THIS is the DDI that killed cerivastatin (withdrawn 2001).
Montelukast (warn): CYP2C8 inhibition. Karonen 2012 (PMID:21838784) verbatim: "The CYP2C8 inhibitor gemfibrozil increased the AUC(0,∞) of montelukast 4.3-fold and its t(1/2) 2.1-fold (P < 0.001)". 11 healthy subjects, randomized crossover (gemfibrozil 600 mg bid / itraconazole / placebo × 5d) + 10 mg PO montelukast d3. AUC ratio 4.30×; Ki ≈ 35/3.30 = 10.6 µM.
Pioglitazone (caution): CYP2C8 inhibition. Jaakkola 2005 (PMID:15900286) verbatim: "Gemfibrozil alone raised the mean total area under the plasma concentration-time curve from time 0 to infinity [AUC(0-infinity)] of pioglitazone 3.2-fold (range, 2.3-fold to 6.5-fold; P < .001)". 12 healthy volunteers, randomized double-blind 4-phase crossover (gemfibrozil/itraconazole), 15 mg PO pioglitazone. AUC ratio 3.20×; Ki ≈ 35/2.20 = 15.9 µM.
Rosiglitazone (caution): CYP2C8 inhibition. Niemi 2003 (PMID:12898007) verbatim: "Gemfibrozil raised the mean area under the plasma rosiglitazone concentration-time curve (AUC) 2.3-fold (range 1.5- to 2.8-fold; p=0.00002)". 10 healthy volunteers, randomized crossover, gemfibrozil 600 mg bid × 4d + 4 mg PO rosiglitazone d3. AUC ratio 2.30×; Ki ≈ 35/1.30 = 26.9 µM. t½ prolonged 3.6 → 7.6 h.
Loperamide (caution): CYP2C8 inhibition (also CYP3A4 + P-gp substrate, so attribution approximate). Niemi 2006 (PMID:16758263) verbatim: "Gemfibrozil raised the Cmax of loperamide 1.6-fold (0.9-3.2; P < 0.05) and its AUC(0-infinity) 2.2-fold (1.0-3.7; P < 0.05)". 12 healthy volunteers, randomized 4-phase crossover, gemfibrozil 600 mg bid × 5d + 4 mg PO loperamide d3. AUC ratio 2.20×; Ki ≈ 35/1.20 = 29.2 µM.