Wavelength-dependent effects of benzoporphyrin derivative monoacid ring A in vivo and in vitro.

Benzoporphyrin derivative monoacid ring A (BPD-MA) is a chlorin-like photosensitizer currently in clinical trials for cancer and psoriasis. It has maximal absorption peaks at both 630 and 690 nm and can be activated at both these wavelengths. In vitro phototoxicity tests using the P815 murine mastocytoma cell lines conducted over wavelengths of light between 678 and 700 nm emitted by an argon-ion pumped dye laser showed that equivalent cell kill could be achieved between 682 and 690 nm. Tests on in vivo phototoxicity of normal skin of DBA/2 mice injected with 2 mg/kg of BPD-MA and exposed to light at 125 J/cm2, between 620 and 700 nm, demonstrated peaks of normal skin damage occurring at 630-640 nm and 680-690 nm. In tests carried out with light between 620 and 700 nm, at 10 nm increments, it was seen that light delivered at 680-690 nm caused slightly more damage to normal skin than light delivered at 630-640 nm. When lower doses of light between 675 and 705 nm were tested using smaller increments, it was determined that equivalent skin damage occurred over a range of 680-695 nm. Antitumor efficacy in tumor-bearing DBA/2 mice was tested between 683 and 695 nm. It was found that equivalent antitumor efficacy, determined by assessing tumor-free status at 20 days posttreatment, occurred at wavelengths between 685 and 693 nm.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of route and frequency of administration of three antimicrobial drugs in cattle.

This study in six cows compared serum concentrations of trimethoprim and sulphadoxine (16 mg/kg body weight (BW)) after once daily and twice daily administration, and of procaine penicillin G (20,000 IU/kg BW) after subcutaneous (SQ) and intramuscular (IM) administration, and evaluated postmortem tissue concentrations of penicillin following SQ treatment. Trimethoprim and penicillin were measured microbiologically, and sulphadoxine colorimetrically. Using minimum inhibitory concentrations (MIC), trimethoprim reached serum concentrations above 0.5 mug/mL from 15 minutes to 120 minutes, and sulphadoxine exceeded 9.5 mug/mL from 10 minutes to 12 hours, after administration. At 24 hours after treatment, both had declined to below the MIC of most organisms. A second treatment at 12 hours maintained concentrations of sulphadoxine above 9.5 mug/mL for a further 24 hours. For penicillin administered IM and SQ, concentrations that peaked at 0.88 mug/mL would inhibit most common grampositive bacteria for the entire 24 hour period and fastidious gram-negative organisms from 90 minutes to 12 hours after SQ treatment, but for virtually the entire period after IM administration. Mean +/- SD concentrations (mug/mL) of penicillin at euthanasia, five days after the last SQ administration, were 1.15 +/- 1.27 (injection site), 1.00 +/- 0.80 (liver), 0.90 +/- 0.58 (renal cortex), 0,58 +/- 0.17 (renal medulla), 0.13 +/- 0.11 (diaphragm), 0.10 +/- 0.08 (gluteal muscle), and 0.06 +/- 0.04 (fat). Therefore, except for the most sensitive organisms, twice daily injection of trimethoprim/sulphadoxine (16 mg/kg BW) may be required. Penicillin G administered SQ at 20,000 IU/kg BW should provide effective serum levels for as long as IM administration against gram-positive organisms, but for only about half as long against gram-negative bacteria. The label withdrawal time of five days cannot be used when penicillin is given SQ at 20,000 IU/kg BW for three days.