The effect of isotretinoin on biotinidase activity.
BACKGROUND
Among the reaction and effects of isotretinoin, mucocutaneous reactions, xerosis and erythema of the skin as well as elevation of liver enzymes and lipids except high density lipoprotein have been reported.


OBJECTIVE
Since biotinidase is mainly produced in the liver and partial biotinidase deficiency causes dermatological manifestations, seborrheic dermatitis, alopecia etc., isotretinoin side effects in relation to biotinidase activity were studied.


METHODS
Forty-two (n = 42) patients with severe cystic acne had liver function tests, lipid estimations, serum biotin as well as biotinidase activity evaluations before (value 1) and on the 30th day (value 2) of treatment with isotretinoin monotherapy (Roaccutane 0.5 mg/kg/24 h). The same laboratory tests were evaluated in 50 controls only once. Moreover, the effect of isotretinoin on a known plasma biotinidase activity was evaluated after incubation in vitro with various concentrations of the drug.


RESULTS
A statistically significant elevation of liver enzymes and lipids, except high density lipoprotein, was observed at the end of this study. On the contrary, biotinidase activity was found to be significantly decreased as compared to the initial values (value 1 = 4.70 +/- 0.89 nmol/min/l, value 2 = 2.50 +/- 0.8 nmol/min/l, p < 0.001) and to controls (5.2 +/- 0.9 nmol/min/l vs. value 2 = 2.50 +/- 0.8 nmol/min/l, p < 0.001). Additionally, biotin levels showed no significant alterations and the in vitro incubation of the enzyme with various concentrations of the drug exhibited no effect on its activity.


CONCLUSIONS
It is suggested that isotretinoin isomers-metabolites act in the liver, resulting in low biotinidase activity.
D000152:Acne Vulgaris / Q000188:drug therapy; D000581:Amidohydrolases / Q000097:blood / Q000378:metabolism*; D001710:Biotin / Q000378:metabolism*; D043523:Biotinidase; D004305:Dose-Response Relationship, Drug; D005260:Female; D005470:Fluorometry; D006801:Humans; D015474:Isotretinoin / Q000009:adverse effects*; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008111:Liver Function Tests; D008297:Male