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Hair Loss Study Abstract: Potentializing effect of ketoconazole on cyclosporin A-induced inhibition of keratinocyte DNA synthesis.
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Title
Potentializing effect of ketoconazole on cyclosporin A-induced inhibition of
keratinocyte DNA synthesis.
Author
Amsellem C; Haftek M; Thivolet J; De Doncker P; Schmitt D
Address
INSERM U 346 affiliée CNRS, Department of Dermatology, E. Herriot Hospital, Lyon,
France.
Source
Acta Derm Venereol, 74: 4, 1994 Jul, 257-9
Abstract
Keratinocyte growth in vitro and DNA synthesis by epidermal cells in vivo are inhibited
by therapeutic doses of cyclosporin A (CsA). This effect may be potentialized by topical
treatment with ketoconazole, since this drug has been shown to inhibit CsA metabolism.
Normal human skin grafts on nude mice receiving intraperitoneal injections of CsA were
treated with ketoconazole cream or its placebo for 3 weeks. The keratinocyte DNA synthesis
rate was evaluated through the rates of bromodeoxyuridine (BrdU) incorporation, and the
trough blood levels of CsA were checked at the end of the experiment. Counting of the
BrdU-labelled nuclei in human tissue sections confirmed a dose-dependent inhibition of
BrdU incorporation by keratinocytes exposed to CsA. This CsA-induced inhibition was
further increased in the animals treated with ketoconazole cream. This effect was best
seen in the groups treated with the low-to-medium doses of CsA (12.5 and 25 mg/kg/day).
However, the simultaneous increase in the circulating CsA levels was also observed in
these animals. Based on our results, we speculate that the potentializing effect of
ketoconazole on CsA-induced inhibition of keratinocyte DNA synthesis is systemic rather
than local.
Language of Publication
English
Unique Identifier
95066569
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