Pharmacokinetics-Based Safety Evaluation in Half-Dose Verteporfin Photodynamic Therapy

초록

Introduction: This study was conducted to assess the systemic pharmacokinetic profiles of half-dose verteporfin photodynamic therapy (PDT) using concentration data from a previous clinical trial and to subsequently suggest safety precaution guidelines. Methods: Coefficients for the bi-exponential model were obtained from published data on post-infusion plasma verteporfin concentrations within a period of 0.17-4 h. Using the extrapolative forecasting method, we plotted the 48-h post-verteporfin plasma concentration model. The time required to achieve a comparable level of verteporfin 48 h after a conventional dose (6 mg/m2 body surface area, BSA) infusion was calculated for a half-dose infusion (3 mg/m2 BSA). Results: At 24 and 48 h post-verteporfin infusion, the plasma concentration following the conventional dose was 1.28 x 10(-4) mu g/mL and 5.06 x 10(-8) mu g/mL, compared to 3.57 x 10(-5) mu g/mL and 7.54 x 10(-9) mu g/mL for the half-dose PDT, representing concentrations that were 3.6 times and 6.7 times higher, respectively. The estimated time required to attain the same level of verteporfin 48 h after a conventional dose was calculated as 42-h post-half-dose PDT. Conclusions: The results of this study indicate that precautionary measures should be taken to avoid sunlight following both half and conventional doses of PDT during the similar post-treatment periods of two days. Nevertheless, given the substantially higher plasma concentration levels associated with conventional-dose PDT compared with the half-dose, systemic safety should be carefully considered when administering conventional-dose PDT.

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