Mark A. Martens

SELECTING OPTIMAL DOSAGE VOLUMES FOR EYE IRRITATION TESTS IN THE RABBIT

AbstractThe elimination kinetics of sodium fluorescein applied into the conjunctival sac of the rabbit eye was studied at two dosages, 100 μl and 50 μl Tear samples were taken during the first 30 min after application. The concentration of sodium fluorescein in the sample was determined using high performance liquid chromatography with UV-VIS detector. The pharmacokinetic parameters were calculated on computer with the ESTRIP program. From the results of this study it can be concluded that the drainage kinetics of sodium fluorescein consist of a rapid and a slow phase. After application of 100 μl into the conjunctival sac of the eye, a time lag was observed before the concentration started to decrease in the eye. The time lag of 5–8 min observed at 100 μl disappeared when a volume of 50 μl was applied. This difference in time lag is indicative for the difference in eye toxicity, which has been observed between dosage volumes of 100 μl and 50 μl in earlier studies. The other pharmacokinetic parameters were...