DETERMINATION OF THE SERUM-PROTEIN BINDING OF OXYCODONE AND MORPHINE USING ULTRAFILTRATION

Protein binding of oxycodone and morphine in human serum was determine d in vitro using ultrafiltration. Binding studies were also performed using both purified human serum albumin and human alpha1-acid glycopro tein (AAG). Albumin was found to be the major binding protein for both oxycodone and morphine. The serum protein binding of both oxycodone a nd morphine was independent of drug concentration in the therapeutic r ange (5-100 ng/ml), but was dependent on protein concentration. In add ition, bound fractions of oxycodone and morphine increased with increa sing concentrations of both albumin and AAG. At physiological pH and t emperature, the mean (+/-SD) serum protein binding of oxycodone was 45 .1% (+/-0.4%) and that of morphine was 35.3% (+/-0.2%) A decrease in t emperature from 37 to 23-degrees-C significantly increased the serum p rotein binding of oxycodone and morphine by 8-9% (p < 0.0001) and 7-10 % (p < 0.0001), respectively, indicating the importance of maintaining the temperature at 37-degrees-C during protein binding experiments. A reduction in pH from 7.75-8.85 to 7.4 significantly reduced serum pro tein binding of both oxycodone and morphine by 4-5% (p < 0.0001) and 4 -7% (p < 0.0001), respectively. Serum samples, to which known concentr ations of oxycodone had been added and which were stored at -20-degree s-C, showing a gradual but significant decline (p < 0.0001) in serum p rotein binding of oxycodone from approximately 45 to 39% during the 4- week storage period. Although serum protein binding of oxycodone and m orphine is dependent on protein concentration and pH-factors that may vary in different disease states-any changes in the binding of oxycodo ne or morphine are unlikely to alter the pharmacological effects of th ese drugs because of their normally low extent of binding (45 and 35%, respectively).