Serum protein binding of noscapine: influence of a reversible hydrolysis

The binding of the antitussive drug noscapine to human serum, pure albumin and alpha 1-acid glycoprotein has been investigated by ultrafiltration and equilibrium dialysis, using radiolabelled noscapine. The binding in serum pooled from volunteers was 93 +/- 0.2% (at 100 ng mL-1). After incubation for 24 h the binding decreased to about 85% (ultrafiltration 87.0 +/- 1.0%; equilibrium dialysis 84.3 +/- 1.2%), because of the conversion of noscapine to noscapinic acid. Only unbound drug underwent this hydrolysis, and as noscapine is extensively bound in healthy volunteers, this elimination process is probably unimportant. The major binding protein of noscapine was albumin (K = 3060 M-1, n = 5.62), but the binding to alpha 1-acid glycoprotein was also substantial (K = 31,500 M-1, n = 1.73). The interindividual variation in binding was low and binding was linear at the concentrations observed after therapeutic doses (0-500 ng mL-1).