The Clinical Pharmacokinetics Section (CPS) is attempting to characterize the pharmacokinetic parameters for several novel anticancer agents that are being clinically evaluated. Most of these agents specifically target the aberrant biology of neoplasms, e.g., altered signal transduction pathways or peptide growth factors involved in the genesis of the malignant phenotype. The successful development of such agents requires the use of pharmacokinetic and pharmacodynamic concepts to a greater extent than what is needed for cytotoxic agents. Each interaction of a cytotoxic drug with its target results in damage, so it is not surprising that oncologists typically are only required to consider the dose of these drugs. This method fails with drugs that interact with their targets or receptors in a reversible manner. The effects of such drugs parallel receptor occupancy, and by extension, the concentrations of these compounds in tissue and plasma are important for activity. Within the CPS we are utilizing compartmental and non-compartmental methods to define the therapeutic range for these agents. Moreover, several of our clinical trials are now utilizing adaptive control with feedback mechanisms. The drugs with which this Section has had the greatest experience include: suramin, phenylacetate, phenylbutyrate, high-dose lovastatin, TNP-470, PSC833, CAI, DAB486IL2, IgS-RFB-4-SMPT-dgA CD22, and ormaplatin.
