Protein binding of indomethacin, methotrexate and morphine in patients with cancer

The in vitro protein binding of indomethacin, morphine and methotrexate has been studied in two groups of ten patients each suffering from different types of cancers and compared with twenty normal adult subjects. One group of patients had active disease and the other group was in complete clinical remission. Serum samples were obtained from each subject and the concentrations of albumin and alpha-1 acid glycoprotein (AGP) were measured. Protein binding of drugs was determined using equilibrium dialysis. Alpha-1 acid glycoprotein levels were increased in patients and this effect was more pronounced in active disease (1802 +/- 1025 mg/l) than in remission (931 +/- 273 mg/l). Albumin levels were reduced in active disease (47.67 +/- 15.91 milligrams), but not in remission (61.86 +/- 6.62 milligrams), as compared to control values (58.98 +/- 9.9 milligrams). The protein binding of methotrexate and indomethacin were both reduced in active disease (34.17 +/- 7.12% and 96.26 +/- 0.93% respectively) in comparison with normal subjects (39.33 +/- 4.68% and 96.89 +/- 0.47% respectively), but that of morphine was not changed. In patients there was a strong negative correlation between albumin and alpha-1 acid glycoprotein levels (r = -0.75, p < 0.01) but the correlation in controls was not significant. This study found only weak association between the binding of the drugs studied and the protein levels. It is concluded that reduction in methotrexate dose levels may reduce toxicity in patients with active cancer.