Pharmacokinetics of flurbiprofen in man. II. Plasma protein binding.
The plasma protein binding of flurbiprofen was studied using equilibrium dialysis. Dialysis was carried out using plasma samples obtained from five of 15 subjects participating in a crossover bioavailability study. During the course of this study subjects received doses of 100, 200, and 300 mg of flurbiprofen as tablets, and 100 mg as an aqueous solution. Seven samples from each of the four treatments (28 samples/subject) were utilized. An additional 14 samples (seven concentrations prepared in duplicate were prepared using blank plasma obtained from each subject. Concentrations of bound (Cbd) and free (Cfd) flurbiprofen were determined at dialysis equilibrium using a radiotracer technique. Binding curves were constructed for each subject using data obtained from these 42 (28 ex vivo and 14 in vitro) samples. The data was well fitted to a modified Scatchard equation with the addition of a linear term. Although the plasma protein binding of flurbiprofen was nonlinear, within the range of concentrations encountered in the clinical setting, it is minimally so. The Cb/Cf ratio averaged 1524, indicating that in plasma, flurbiprofen is greater than 99.9% bound. The results support the observation that for doses of flurbiprofen usually encountered clinically, the drug obeys linear kinetics.
Szpunar
G J
GJ
Clinical Pharmacokinetics, Upjohn Company, Kalamazoo, MI 49001.
Albert
K S
KS
Wagner
J G
JG
D000328:Adult; D001798:Blood Proteins / Q000378:metabolism*; D003956:Dialysis; D005480:Flurbiprofen / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D011422:Propionates / Q000493:pharmacokinetics*; D011485:Protein Binding
D001798:Blood Proteins; D011422:Propionates; D005480:Flurbiprofen