Protein binding of drugs is an important factor influencing both pharmacoki
netic and pharmacodynamic parameters. Thus, knowing the extent of protein b
inding of drugs is crucial. Centchroman is a non-steroidal once a week oral
contraceptive. It has been reported to be useful for the treatment of brea
st cancer and osteoporosis. Ample data has been generated on pharmacokineti
cs of centchroman in animals and humans. The extent of protein binding of c
entchroman has not been established so far. Non-specific adsorption of the
drug limits the use of conventional methods like ultrafiltration and equili
brium dialysis. A method of charcoal adsorption as reported by Yuan et al.
(method I) was used after modification (method II) to determine its binding
to human serum. The extent of protein binding (%) is estimated from declin
e of percent drug remaining in the supernatant after adding the charcoal. S
tudy was carried out at 1- and 10-mu g/ml concentrations in drug free human
serum samples and an HPLC assay was used to determine concentration-time d
ata. The percentage of centchroman remaining in serum versus time data was
analysed using non-linear fitting programs on WinNonlin software. Method II
was found to give higher estimates of protein binding than the former meth
od by preventing the dilution effect. Using this method, the extent of prot
ein binding of centchroman was found to be 101.83 +/- 1.28 and 94.87 +/- 3.
59% at 1 and 10 mu g/ml, respectively. However, it was similar to 90% in th
e individual serum samples showing intersubject variability in protein bind
ing of centchroman. (C) 1999 Elsevier Science B.V. All rights reserved.