Pharmacokinetics in photodynamic therapy

The innate appeal of photodynamic therapy (PDT) is its promise of selective tumour destruction by the concerted action of a photosensitizing agent and an activating cold light source. These photosensitizers are selectively re tained in tumour tissue as distinct from normal, nonmalignant tissue, as a result of either easier uptake into, or slower elimination from, the former than from the latter. Knowledge of the quantitative kinetic parameters thu s permits, in principle, the selection of an appropriate interval after dru g administration, at which the differential between tumour and normal tissu e concentrations is optimal, and at which the activation of the agent by th e light will produce the greatest damage to the tumour whilst minimizing co ncomitant damage to the nonmalignant tissue. The choice of that time interv al is highly dependent on the chemical and biological properties of the pho tosensitizer, as well as on the exact mechanism involved in tumour kill. To illustrate the complexities associated with these clinical considerations, and the importance of correct interval selection, a full pharmacokinetic i nvestigation was conducted with three second generation photosensitizing dr ugs. These are: temoporfin; a polyethyleneglycol derivative of temoporfin ( PEC-temoporfin); and delta-aminolaevulinic acid (ALA). It is shown that a d ynamic pharmacokinetic evaluation of the plasma and tissue contents, follow ed by a static biodistribution study of these agents, can provide values fo r kinetic parameters which are helpful in defining the optimal clinical tre atment protocol. However, it is pointed out that there are difficulties in translating such parameters as drug dose, time interval and activating ligh t dose between species, and that human physiology may complicate the select ion even further. it is, however, demonstrated that pharmacokinetic studies are an essential prerequisite for the precise specification of an optimal therapeutic protocol for any photosensitizer, which will permit the achieve ment of good efficacy with a minimum of adverse reactions for the patient.