Drug metabolites produced in vivo promote accelerated clearance of platelets by metabolite-specific DDAbs. Human platelets suspended in serum containing DDAbs specific for acetaminophen glucuronide (A) or naproxen glucuronide (B) were infused into NOD/scid mice. Acetaminophen (50 mg/kg) or naproxen (75 mg/kg) were injected intraperitoneally at 0 and 5 hours. Platelet survival was significantly shortened in mice given DDAb and the unmodified primary drug (triangles) but not in mice given DDAb (squares) or drug with normal serum (circles). Values shown are the average of triplicate experiments ± 1 SEM. *P < .05, **P < .01, ***P < .001 relative to controls.