3 research outputs found
In-vitro lymphocyte toxicity to a phenytoin metabolite in phenytoin induced cutaneous adverse drug eruptions
BACKGROUND: Phenytoin, one of the most commonly used antiepileptic
drug, is associated with a wide spectrum of adverse drug eruptions. It
is metabolized by the hepatic microsomal enzymes. The intermediate
metabolites are arene oxides which accumulate due to deficiency of the
enzyme epoxide hydrolase. These are postulated to be associated with
phenytoin induced hepatotoxicity and antiepileptic hypersensitivity
syndrome. AIM: We tried to correlate the in vitro lymphocyte toxicity
of arene oxide metabolites with phenytoin induced drug eruptions and
hence develop it as a predictive test for the same. METHODS:
Clinically diagnosed cases of phenytoin induced drug eruptions were
selected in this hospital based study. Lymphocytes from the subjects
and controls were exposed to the phenytoin metabolites generated by a
murine hepatic microsomal system. The toxicity was assayed by trypan
blue dye exclusion test. The results were analyzed by a linear
orthogonal curve and were compared for the subject and control.
RESULTS: The results showed increased toxicity to lymphocytes from the
patients when compared to those from controls. The toxicity was
directly proportional to the severity of the drug eruption.
CONCLUSION: In vitro lymphocyte cytotoxicity to phenytoin metabolites
tested in this animal system could possibly predict phenytoin induced
drug eruptions
In-vitro lymphocyte toxicity to a phenytoin metabolite in phenytoin induced cutaneous adverse drug eruptions
BACKGROUND: Phenytoin, one of the most commonly used antiepileptic drug, is associated with a wide spectrum of adverse drug eruptions. It is metabolized by the hepatic microsomal enzymes. The intermediate metabolites are arene oxides which accumulate due to deficiency of the enzyme epoxide hydrolase. These are postulated to be associated with phenytoin induced hepatotoxicity and antiepileptic hypersensitivity syndrome. AIM: We tried to correlate the in vitro lymphocyte toxicity of arene oxide metabolites with phenytoin induced drug eruptions and hence develop it as a predictive test for the same. METHODS: Clinically diagnosed cases of phenytoin induced drug eruptions were selected in this hospital based study. Lymphocytes from the subjects and controls were exposed to the phenytoin metabolites generated by a murine hepatic microsomal system. The toxicity was assayed by trypan blue dye exclusion test. The results were analyzed by a linear orthogonal curve and were compared for the subject and control. RESULTS: The results showed increased toxicity to lymphocytes from the patients when compared to those from controls. The toxicity was directly proportional to the severity of the drug eruption. CONCLUSION: In vitro lymphocyte cytotoxicity to phenytoin metabolites tested in this animal system could possibly predict phenytoin induced drug eruptions