Gene therapy pharmacokinetics

Clinical trial methodology and guidelines for special disease-related therapeutie fields are discussed. In cooperation with other working parties, guidanee for modified-release oral and transdermal dosage forms, pharmacokinetics, and clinical investigation of new vaccines, gene therapy, and cell-cultured influenza vaeeines has been... 

Ad.TNF gene therapy is presently in clinical trials in patients receiving radiotherapy. An open-label, phase I, dose-escalation study of tumor necrosis factor-alpha (TNFerade) gene transfer with radiation therapy for locally advanced, recurrent, or metastatic solid tumors is currently accruing patients and has several endpoints (82), including toxicity and tolerable dose. Pharmacokinetics will be evaluated and biological correlates will determine the histologic response to therapy. 

The pharmacokinetics of a gene drug within tumor tissue is a very important issue because cancer becomes one of the major targets for gene therapy, and various protocols are now under clinical trials (Roth and Cristiano, 1997). For in vivo gene delivery protocols, a gene drug, free or complexed with vector, is sometimes... 

Z.Y. Yang, D. Laface, S.H. Gromkowski, and G.J. Nabel. 1995. Cancer gene therapy using plasmid DNA pharmacokinetic study of DNA following injection in mice. Hum. Gene Ther. 6 553-564. 

Mahato, R.I., Takakura, Y. and Hashida, M. (1997) Nonviral vectors for in vivo gene therapy Physicochemical and pharmacokinetic considerations. Crit. Rev. Ther. Drug Carrier Syst, 14 133-172. 

Harada-Shiba M, Yamauchi K, Harada A, Takamisawa I, Shkno-kado K, Kataoka K (2002) Polyion complex micelles as vectors in gene therapy-pharmacokinetics and in vivo gene transfer. Gene Ther 9 407 14. 

Table 22.1 Pharmacokinetic considerations for gene therapy agents [Adapted from Ledley TS, Ledley FD. 1994. Multicompartment numerical model of cellular events in the pharmacokinetics of gene therapies. Hum. Gene Ther. 5 679-691]...

Table 17.1 Pharmacokinetic considerations for gene therapy agents...

The pharmacokinetics of gene therapy, and its relationship to dynamic effects, are very different form the orthodox pharmaceutical situation (Table... 

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