Skip to main content

Pharmacokinetic analysis of two-step approaches using bifunctional and enzyme-conjugated antibodies.

Publication ,  Journal Article
Yuan, F; Baxter, LT; Jain, RK
Published in: Cancer research
June 1991

Bifunctional antibodies (BFA) and enzyme-conjugated antibodies (ECA) can be used to preferentially deliver a hapten or drug to tumor sites for diagnosis and therapy. We present here a simple pharmacokinetic model for the above two systems by considering only two compartments, the plasma and tumor. The models predict that the longer the time delay between the BFA and hapten or between the ECA and prodrug injections, the higher the tumor:plasma concentration ratio of the hapten or drug. In addition, multiple injections of the hapten or prodrug is predicted to give a more uniform concentration of the hapten or drug in both the tumor and plasma than bolus injection. We suggest that, initially, the most effective dose of BFA should be selected and then the hapten concentration chosen accordingly. The decrease of the ECA injection dose would increase the tumor:plasma concentration ratio of the drug and yet decrease the tumor concentration of the drug. In clinical application of the ECA system, consideration of ECA dose should be balanced between the tumor concentration and the tumor:plasma concentration ratio of the drug. The dose of the prodrug injection is suggested to be equal to the required toxic concentration of the drug in the tumor. There are several ways to improve the tumor:plasma concentration ratio of the hapten or drug, such as changing the binding kinetics of the antibody to tumor or the hapten to BFA and removing the antibody from the plasma before the injection of the hapten or prodrug. One notable difference between the BFA and ECA approaches is that there is an upper limit for maximum hapten concentration in the former, and hence, from the point of drug delivery alone the latter approach is presumably superior. The limitations of the models and therapeutic implications are also discussed.

Duke Scholars

Published In

Cancer research

EISSN

1538-7445

ISSN

0008-5472

Publication Date

June 1991

Volume

51

Issue

12

Start / End Page

3119 / 3130

Related Subject Headings

  • Time Factors
  • Oncology & Carcinogenesis
  • Neoplasms
  • Models, Biological
  • Mathematics
  • Kinetics
  • Humans
  • Haptens
  • Enzymes
  • Enzyme Therapy
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yuan, F., Baxter, L. T., & Jain, R. K. (1991). Pharmacokinetic analysis of two-step approaches using bifunctional and enzyme-conjugated antibodies. Cancer Research, 51(12), 3119–3130.
Yuan, F., L. T. Baxter, and R. K. Jain. “Pharmacokinetic analysis of two-step approaches using bifunctional and enzyme-conjugated antibodies.Cancer Research 51, no. 12 (June 1991): 3119–30.
Yuan F, Baxter LT, Jain RK. Pharmacokinetic analysis of two-step approaches using bifunctional and enzyme-conjugated antibodies. Cancer research. 1991 Jun;51(12):3119–30.
Yuan, F., et al. “Pharmacokinetic analysis of two-step approaches using bifunctional and enzyme-conjugated antibodies.Cancer Research, vol. 51, no. 12, June 1991, pp. 3119–30.
Yuan F, Baxter LT, Jain RK. Pharmacokinetic analysis of two-step approaches using bifunctional and enzyme-conjugated antibodies. Cancer research. 1991 Jun;51(12):3119–3130.

Published In

Cancer research

EISSN

1538-7445

ISSN

0008-5472

Publication Date

June 1991

Volume

51

Issue

12

Start / End Page

3119 / 3130

Related Subject Headings

  • Time Factors
  • Oncology & Carcinogenesis
  • Neoplasms
  • Models, Biological
  • Mathematics
  • Kinetics
  • Humans
  • Haptens
  • Enzymes
  • Enzyme Therapy