Relación estructura-fotoestabilidad u fototoxicidad de fluoroquinolonas / Structure-photostability and phototoxicity relationship in fluoroquinolones

Las quinolonas constituyen una familia de antibióticos de amplio uso en la actualidad, debido a su gran eficacia clínica en el tratamiento de infecciones del tracto respiratorio, urinario, tejidos blandos y enfermedades de transmisión sexual. De acuerdo a su estructura base se pueden clasificar en quinolonas naftiridínicas (enoxacino y ácido nalidíxico), quinolínicas (ciprofloxacino, norfloxacino, ácido oxolínico, rosoxacino) y pirimido-pirimidinicas (ácido pipemídico). Las quinolonas se caracterizan por presentar reacciones de fotosensibilidad y fotolabilidad. El ácido nalidíxico, quinolona de primera generación, presenta reacciones de fototoxicidad, evaluadas en el modelo del glóbulo rojo y en cultivos celulares. El ácido nalidíxico, exento del sustituyente piperazínico presenta una fotolabilidad disminuida. Las fluoroquinolonas, a diferencia del ácido nalidíxico, presentan un anillo piperazínico o metil piperazínico en posición 7, incorporado con el fin de mejorar las propiedades antibacterianas. En este trabajo se investiga la influencia del anillo piperazínico en posición 7 sobre la fotolabilidad y fototoxicidad, demostrándose que las fluoroquinolonas que poseen este sustituyente presentan una fotolabilidad aumentada y una fototoxicidad disminuída, en relación a quinolonas carentes de éste grupo. Es probable que la fotodegradación de quinolonas transcurra mediante un mecanismo radicalario, con la pérdida del grupo carboxílico

Quinolones constitute a large class of synthetic antimicrobial agents that are highly effective in the treatment of respiratory, urinary, sexually transmitted diseases and soft tissue infection. In agreement with his structure the quinolones can be classified into naftaridines (enoxacin and nalidixic acid), quinolines (ciprofloxacin, norfloxacin, oxolinic acid, roxosacin) and pyrid-pyrimidin (pipemidic acid). Some quinolones may undergo photodegradation reactions. On the other hand, quinolones can induce cutaneous photosensitivity reactions.and photolability as well. Nalidixic acid, a first quinolone generation, may undergo phototoxic effects on the red blood cells and in cell culture. Nalidixic acid, which has not the piperazine group in position 7, exhibit a moderated photolability. The fluoroquinolones as oppossed to nalidixic acid have a piperazine ring in position 7. We investigated the influence of the piperazine ring on the phototoxicity and photolability of several quinolones. We demonstrated that the fluoroquinolones with piperazinic group present higher photolability and less phototoxicity .It is possible that the photodegradation of quinolones takes place through a radical pathway, with the loss of a carboxylic acid group

The effect of infinitesimal drug dilutions on the pharmacokinetics of nalidixic acid and atenolol.

1. Ten healthy subjects received two treatments: a single 1 g oral dose of nalidixic acid (NA) followed 1 h later by either an infinitesimal dilution of the drug (NA 7CH) or by succussed water which served as placebo. The study was repeated 18 months later in 10 different subjects. 2. A further 10 healthy subjects received three treatments: a single 100 mg oral dose of atenolol (AT) followed 3 h later by either placebo or a dilution of AT (AT 7CH) or of bisoprolol (BI 7CH). The homoeopathic preparations were administered by the sublingual route. 3. In the first NA experiment NA 7CH significantly shortened the elimination half-life of NA from 8.6 +/- 2.2 (placebo) to 6.4 +/- 1.6 h (NA 7CH). In the second NA experiment none of the pharmacokinetic parameters was modified significantly by the administration of NA 7CH. Neither AT 7CH nor BI 7CH modified the pharmacokinetics of AT.