Photochemical decomposition of lomefloxacin in vitro and in vivo.
To obtain an idea of the photostability of Lomefloxacin (Lom) under in vivo conditions the compound was exposed to UV-A (310-360 nm) in PBS buffer pH 7.4. Exposure of 10 microg/ml of Lom in PBS pH 7.4 led to more than 50% decomposition within 10 min. Loss of the fluorine atom at C-8 and partial breakdown of the piperazine ring occurred. The only two photoproducts formed under these conditions were AEA, 1-ethyl-6-fluoro-1,4-dihydro-7-(2-aminoethyl-amino)-4-oxo-3-quinolinecarboxylic acid, and APA, 1-ethyl-6-fluoro-1,4-dihydro-7-(2-aminopropyl-amino)-4-oxo-3-quinolinecarboxylic acid. When Lom was exposed in whole blood in vitro, the same photochemical decomposition was observed in the plasma as in PBS buffer: APA and AEA were the only products. During UV-A exposure, Lom was shown to be taken up by the leukocytes. This process appeared to be less rapid during UV-A exposure than in the dark. As soon as UV-A exposure commenced, AEA and APA were found. As in the plasma, the total amount of Lom and the two photoproducts in the leukocytes was not significantly different from the amount of Lom found in unexposed cells at the same time point. The erythrocytes did not take up Lom, but exposure of whole blood to Lom and UV-A under the above conditions led to more than 7% haemolysis. Treatment of rats with a combination of Lom and UV-A demonstrated photodecomposition of Lom in vivo. In urine produced during exposure and by the irradiated rats during the twilight period after exposure, a considerable amount of AEA and APA was found. The blood plasma from rats exposed simultaneously to UV-A and Lom proved to contain AEA and APA and, in the leukocytes, APA. This was not the case with animals kept in twilight.
de Vries
H
H
Gorlaeus Laboratoria - 642HB, Medicinal Photochemistry, Leiden, The Netherlands. h.vries@chem.leidenuniv.nl
van Henegouwen
G M
GM
D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects*; D002021:Buffers; D004912:Erythrocytes / Q000378:metabolism; D024841:Fluoroquinolones; D006461:Hemolysis; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D010777:Photochemistry; D015363:Quinolones / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects*; D051381:Rats; D017208:Rats, Wistar
D000890:Anti-Infective Agents; D002021:Buffers; D024841:Fluoroquinolones; D015363:Quinolones; C053091:lomefloxacin