The effect of isotretinoin on biotinidase activity

Background: Among the reaction and effects of isotretinoin, mucocutaneous r eactions, xerosis and erythema of the skin as well as elevation of liver en zymes and lipids except high density lipoprotein have been reported. Object ive: Since biotinidase is mainly produced in the liver and partial biotinid ase deficiency causes dermatological manifestations, seborrheic dermatitis, alopecia etc., isotretinoin side effects in relation to biotinidase activi ty were studied. Methods: Forty-two (n = 42) patients with severe cystic ac ne had liver function tests, lipid estimations, serum biotin as well as bio tinidase activity evaluations before (value 1) and on the 30th day (value 2 ) of treatment with isotretinoin monotherapy (Roaccutane 0.5 mg/kg/24 h). T he same laboratory tests were evaluated in 50 controls only once. Moreover, the effect of isotretinoin on a known plasma biotinidase activity was eval uated after incubation in vitro with various concentrations of the drug. Re sults: A statistically significant elevation of liver enzymes and lipids, e xcept high density lipoprotein, was observed at the end of this study. On t he contrary, biotinidase activity was found to be significantly decreased a s 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, biot in levels showed no significant alterations and the in vitro incubation of the enzyme with various concentrations of the drug exhibited no effect on i ts activity. Conclusion: It is suggested that isotretinoin isomers-metaboli tes act in the liver, resulting in low biotinidase activity.