Pharmacokinetics of tetra(m-hydroxyphenyl)chlorin in human plasma and individualized light dosimetry in photodynamic therapy
The pharmacokinetics of the photosensitizer 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (mTHPC) was investigated in the plasma of 20 patients by absorption and fluorescence spectroscopy. The temporal behavior was characterized by a rapid decrease in concn. during the first minutes after i.v. injection of 0.15 mg/kg mTHPC. A min. concn. in the plasma was reached after about 45 min. The drug concn. then increased again, attaining a max. after about 10 h, after which it decreased again with a half life of about 30 h. Irradn. tests in the oral cavity at different time intervals after the injection revealed that the tissue reaction was only partially correlated with the mTHPC plasma level. The tissue response was stronger at later drug-light intervals (1-4 days) than during the first hours after injection even though the mTHPC plasma concn. was higher at the shorter times. Relative mTHPC concns. were also measured in the mucosae of the oral cavity, the esophagus and the bronchi of 27 patients by light-induced fluorescence spectroscopy using an optical fiber-based spectrometer. These measurements were performed prior to photodynamic therapy (PDT), 4 days after injection of the photosensitizer. Highly significant linear correlations were found between the relative mTHPC concns. in the mucosae of these three organs. Likewise, the plasma levels of mTHPC measured just before PDT were significantly correlated with the mTHPC concns. in the three types of mucosae mentioned above. These results indicate that mTHPC plasma levels measured just before PDT can be used for PDT light dosimetry.
WOS:000073796300021
1998
67
5
596
602
Copyright 2003 ACS, CAPLUS, AN 1998:350609, CAN 129:78579, 8-9, Radiation Biochemistry, Institute of Environmental Engineering, Swiss Federal Institute of Technology (EPFL),Lausanne,Switz. FIELD URL:, Journal, PHCBAP, written in English., Blood plasma; Dosimetry; Photodynamic therapy; Photosensitizers (tetra(m-hydroxyphenyl)chlorin pharmacokinetics in human plasma and individualized light dosimetry in photodynamic therapy), 1) van Den Bergh, H; Photochemotherapy:Photodynamic Therapy and Other Modalities III, Proc SPIE 1997, 3191, 2|2) Stables, G; Cancer Treatment Rev 1995, 21, 311|3) Schuitmaker, J; J Photochem Photobiol B: Biol 1996, 34, 3|4) Monnier, P; Lasers Med Sci 1990, 5, 149|5) Grosjean, P; Lasers Med Sci 1996, 11, 227|6) Grosjean, P; J Clin Laser Med Surg 1996, 14/5, 281|7) Savary, J; Arch Otolaryngol Head Neck Surg 1997, 123, 162|8) Ris, H; Lasers Surg Med 1996, 18, 39|9) Bonnett, R; Biochem J 1989, 261, 277|10) Wagnieres, G; Photochem Photobiol In press 1998|11) Braichotte, D; Int J Cancer 1995, 63, 198|12) McLeod, H; Handbook of Pharmacokinetic/Pharmacodynamic Correlation 1995, 389|13) Braichotte, D; Lasers Med Sci 1996, 11, 247|14) Braichotte, D; Lasers Surg Med 1996, 19, 340|15) Miller, J; Spectrosc Europe 1992, 4, 26|16) Sun, Y; Clin Chem 1988, 43, 497|17) Glanzmann, T; Optical Biopsies and Microscopic Techniques 1996, 2926, 41|18) Wagnieres, G; Submitted to Photochem Photobiol 1998|19) Taylor, J; An Introduction to Error Analysis, Chapter 9 1982|20) Westermann, P; Int J Cancer In press 1998|21) Barberi, M; J Chromatogr B 1997, 688, 331|22) Lofgren, L; Arch Otolaryngol Head Neck Surg 1994, 120, 1355|23) Whelpton, R; Photochem Photobiol 1995, 61, 397|24) Ma, L; Int J Cancer 1994, 57, 883|25) Egger, N; Pharmacology 1996, 52, 362|26) Glanzmann, T; The Rank Prize Funds, Mini-Symposium on Photodynamic Therapy 1996|27) Ronn, A; Lasers Med Sci 1996, 11, 267|28) Lee, P; Pharmacokinetic Analysis 1996, 213|29) Boyle, R; Photochem Photobiol 1996, 64, 469|30) Maziere, J; J Photochem Photobiol B: Biol 1991, 8, 351|31) Reddi, E; J Photochem Photobiol B: Biol 1997, 37, 189|32) Whelpton, R; Photochem Photobiol 1996, 63, 885|33) Ronn, A; Lasers Surg Med 1997, 20, 437|34) Wang, Q; Biomed Chromatogr 1993, 7, 155|35) Da Silva, M; Photochem Photobiol 1995, 61, 414
REVIEWED
EPFL