UV-induced isomerization of oral retinoids in vitro and in vivo in hairless mice.
Ultraviolet (UV) irradiation causes isomerization and destruction of many vitamin A analogues (retinoids). Using high-performance liquid chromatography (HPLC), we investigated in vitro and in vivo the effects of UV irradiation on 2 all-trans aromatic retinoids (etretinate and acitretin) and on 13-cis retinoic acid (isotretinoin). When etretinate and acitretin dissolved in ethanol were irradiated with UVB (280-320 nm; 10-336 mJ/cm2) or UVA (320-400 nm; 1-5 J/cm2), extensive and reproducible cis-isomerizations occurred at the 13-position (cis/trans ratio approximately 1.6 in all experiments) but there was no progressive photodegradation of the molecules. Irradiation of isotretinoin produced only moderate trans-isomerization but the sum of HPLC peak heights fell with increasing UV doses, being 72% of the original value after 336 mJ/cm2 of UVB. Hairless mice were given etretinate (50 mg/kg bw), acitretin (200 mg/kg) or isotretinoin (50 mg/kg) on days 1, 4 and 7 and were irradiated daily for 8 d with 13 mJ/cm2 UVB plus 1 J/cm2 UVA. Samples of serum, dorsal skin and liver were collected and retinoids analyzed by HPLC. In the etretinate and acitretin-treated, irradiated animals the serum concentrations of the 13-cis isomers were 2-6 times higher than in nonirradiated controls. Irradiated epidermis also contained significantly higher concentrations of 13-cis etretinate and 13-cis acitretin than did control epidermis. The serum and epidermal concentrations of all-trans etretinate and acitretin were unchanged or even increased after irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)
Berne
B
B
Department of Dermatology, University Hospital, Uppsala, Sweden.
Rollman
O
O
Vahlquist
A
A
D017255:Acitretin; D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004307:Dose-Response Relationship, Radiation; D005050:Etretinate / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000528:radiation effects; D005260:Female; D066298:In Vitro Techniques; D007536:Isomerism; D015474:Isotretinoin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000528:radiation effects; D051379:Mice; D008812:Mice, Hairless; D012176:Retinoids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000528:radiation effects*; D012867:Skin / Q000528:radiation effects; D014212:Tretinoin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics / Q000528:radiation effects; D014466:Ultraviolet Rays
D012176:Retinoids; D014212:Tretinoin; D005050:Etretinate; D015474:Isotretinoin; D017255:Acitretin