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Elevated plasma homocysteine levels in patients on isotretinoin therapy for cystic acne

Authors

  • Kleopatra H. Schulpis MD, PhD,

    1. From the Institute of Child Health, and Pharmacokinetics and Parenteral Nutrition Unit, Aghia Sophia Children's Hospital, Athens, Greece, the Dermatology Clinic, Athens University, ‘A. Syngros’ Hospital, Athens, Greece, and the Experimental Physiology Department Medical School, Athens University, Athens, Greece
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  • George A. Karikas Pharm D, PhD,

    1. From the Institute of Child Health, and Pharmacokinetics and Parenteral Nutrition Unit, Aghia Sophia Children's Hospital, Athens, Greece, the Dermatology Clinic, Athens University, ‘A. Syngros’ Hospital, Athens, Greece, and the Experimental Physiology Department Medical School, Athens University, Athens, Greece
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  • Sophia Georgala MD, PhD,

    1. From the Institute of Child Health, and Pharmacokinetics and Parenteral Nutrition Unit, Aghia Sophia Children's Hospital, Athens, Greece, the Dermatology Clinic, Athens University, ‘A. Syngros’ Hospital, Athens, Greece, and the Experimental Physiology Department Medical School, Athens University, Athens, Greece
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  • Timos Michas MD,

    1. From the Institute of Child Health, and Pharmacokinetics and Parenteral Nutrition Unit, Aghia Sophia Children's Hospital, Athens, Greece, the Dermatology Clinic, Athens University, ‘A. Syngros’ Hospital, Athens, Greece, and the Experimental Physiology Department Medical School, Athens University, Athens, Greece
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  • Stylianos Tsakiris PhD

    1. From the Institute of Child Health, and Pharmacokinetics and Parenteral Nutrition Unit, Aghia Sophia Children's Hospital, Athens, Greece, the Dermatology Clinic, Athens University, ‘A. Syngros’ Hospital, Athens, Greece, and the Experimental Physiology Department Medical School, Athens University, Athens, Greece
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Kleopatra H. Schulpis, md, phd
Institute of Child Health
Aghia Sophia Children's Hospital
115 27 Athens
Greece

Abstract

Abstract

Background The use of Isotretinoin (Iso) for cystic acne (CA) therapy includes marked side-effects such as dyslipidemia, increased liver enzymes, and reduction of biotinidase activity. Moreover, Homocysteine (Hcy), an amino acid, is metabolized in the liver requiring folate, vitamin B6, vitamin B12, and the activity of enzymes, i.e. cystathionine-β-synthase. Increased blood levels of Hcy are associated with premature occlusive vascular disease.

Objective The aim of this study was the evaluation of Hcy levels and the responsible vitamins for its metabolism in patients with CA on Iso treatment.

Methods  and Results  Twenty-eight patients with CA were submitted to laboratory examinations before (Value 1) and after (Value 2) 45 days on Iso (0.5 mg/kg/24 h) therapy. Blood levels of Hcy and vitamin B6 were evaluated by HPLC methods, and folate and vitamin B12 using a commercial Kit. Hcy levels (Value 1 = 7.86 ± 1.6 μmol/L; Value 2 = 13.65 ± 3.3 μmol/L; P < 0.001) were statistically significantly increased in patients on treatment. Vitamins were unaltered, and lipids and liver enzymes increased. Significant correlation between Hcy levels, vitamins, and liver enzymes was found. Methionine loading tests performed in nine patient-volunteers showed an abnormal response post-treatment.

Conclusions  It is suggested that the elevated Hcy levels in patients after 45 days on Iso therapy could be due either to the ‘inhibition’ of cystathionine-β-synthase by the drug and/or their liver dysfunction. Daily vitamin supplementation along with frequent evaluations of Hcy blood levels are recommended for the prevention of a premature occlusive vascular disease.

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