Effect of drugs and cocaine metabolites on cocaine and cocaethylene binding to human serum in vitro.

The effect of amphetamine (AMPH), codeine (COD), methamphetamine (MEPH), morphine (MORP), and benzoylecgonine (BE) on the binding of cocaethylene (CE) and cocaine (COC) to human serum in vitro was investigated by equilibrium dialysis at 4 degrees C. Each compound was added individually at concentrations of 500, 1,000, or 2,000 nM to pooled human serum containing COC or CE at 500 nM concentration. For COC, the addition of COD, MEPH, and CE enhanced serum binding whereas MORP and BE decreased it. Variable effects on COC binding were noted for AMPH. For CE, the addition of COD and COC generally increased binding whereas MORP decreased it. No appreciable effect on CE binding was observed after adding AMPH, MEPH, and BE. Except for CE, AMPH, and MEPH in the presence of COC, the binding of COC and CE tended to be less with 2,000 nM of each added drug than at lower concentrations of them, presumably because of mass-action displacement of COC and CE at the higher concentration. These findings should be clinically important because these drugs are frequently found together in patients.