Summary
We investigated the differences in plasma protein binding of flavone acetic acid (FAA) in mice and men in an attempt to explain the inter-species differences in response. In vitro data indicate both qualitative and quantitative differences in FAA protein binding: approximately 80% is bound in humans, with two different types of binding site identified; in mice, 70% is bound and only one binding site could be described. Protein binding is dose-dependent in both species. Plasma samples from 20 patients receiving FAA showed that most achieved levels that would be active in mice. We conclude that these differences in protein binding are insufficient to explain totally the observed differences in response.
This is a preview of subscription content, log in via an institution to check access.
References
Belforte G, Bona B, Milanese M (1984) Advanced modeling and identification techniques for metabolic processes. CRC Crit Rev Biomed Eng 10(4): 275
Bibby MC, Double JA, Phillips RM, Loadman PM (1987) Factors involved in the anti-cancer activity of the investigational agents LM985 (flavone acetic acid ester) and LM975 (flavone acetic acid). Br J Cancer 55: 159
Corbett TH, Bissery MC, Wozniak A, Plowman J, Polin L, Tapazoglou E, Dieckman J, Valeriote F (1986) Activity of flavone acetic acid (NSC-347512) against solid tumours of mice. Invest New Drugs 4: 207
Kerr DJ, Kaye SB, Cassidy J, Bradley C, Rankin EM, Adams L, Setanoians A, Young T, Forrest G, Soukop M, Clavel M (1987) A phase I and pharmacokinetic study of flavone acetic acid. Cancer Res 47: 6776
Plowman J, Narayanan V, Dykes D, Szarvasi E, Briet P, Yoder OC, Paull K (1986) Flavone acetic acid (NSC-347512), a novel agent with preclinical antitumour activity against colon adenocarcinoma 38 in mice. Cancer Treat Rep 70: 631
Scatchard G (1949) The attractions of proteins for small molecules and ions. Ann NY Acad Sci 51: 660
Zaharko DS, McCormack JJ (1987) A binding isotherm useful for predicting free drug in-vivo. Pharmacologist 29(3): 74
Zaharko DS, Grieshaber CK, Plowman J, Craddock JC (1986) Therapeutic and pharmacokinetic relationships of flavone acetic acid: an agent with activity against solid tumours. Cancer Treat Rep 70(12): 1415
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cassidy, J., Kerr, D.J., Setanoians, A. et al. Could interspecies differences in the protein binding of flavone acetic acid contribute to the failure to predict lack of efficacy in patients?. Cancer Chemother. Pharmacol. 23, 397–400 (1989). https://doi.org/10.1007/BF00435845
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00435845