title: Low levels of alitretinoin in seminal fluids after repeated oral doses in healthy men.
abstract: BACKGROUND
  Alitretinoin, like all retinoids, is teratogenic, and can only be given to women of childbearing potential if pregnancy is excluded and a strict contraceptive programme is followed.
  
  
  OBJECTIVE
  This study was designed to determine whether alitretinoin in the semen of men treated with alitretinoin poses a teratogenic risk to their female partners.
  
  
  METHODS
  In total, 24 healthy men aged 18-45 years received alitretinoin 20 mg (n = 12) or 40 mg (n = 12), once daily for 14 days. Subjects in the 40 mg dose group provided ejaculate at baseline, on day 1, before and approximately 4 h after dosing on day 2, and at follow-up on study day 21 (± 2).
  
  
  RESULTS
  Alitretinoin and 4-oxo-alitretinoin were detected in 11 of the 12 semen samples. The highest level of alitretinoin in semen was 7.92 ng/mL. Assuming an ejaculate volume of 10 mL, the amount of drug transferred in semen would be about 80 ng, 1/375,000 of a single 30 mg capsule. Complete absorption of 80 ng of alitretinoin from semen, presuming a volume of distribution confined to 5 L of circulating blood in the partner, would lead to an increase in plasma alitretinoin concentration of 0.016 ng/mL, which appears to be negligible compared with measured endogenous plasma levels. Increases in plasma levels of related retinoids are also negligible.
  
  
  CONCLUSIONS
  Alitretinoin in the semen of men receiving up to 40 mg of oral alitretinoin per day is unlikely to be associated with teratogenic risk in their female partners. Barrier contraception is therefore not required for men taking alitretinoin.
authors: Basilea Pharmaceutica International Ltd, Basel, Switzerland.
authors: A H
authors: AH
authors: Schmitt-Hoffmann
authors: B
authors: B
authors: Roos
authors: J
authors: J
authors: Sauer
authors: T
authors: T
authors: Brown
authors: E
authors: E
authors: Weidekamm
authors: I
authors: I
authors: Meyer
authors: M
authors: M
authors: Schleimer
authors: J
authors: J
authors: Maares
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000077556:Alitretinoin; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment / Q000379:methods; D012661:Semen / Q000378:metabolism*; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D003879:Dermatologic Agents; D000077556:Alitretinoin; D014212:Tretinoin