Potentializing effect of ketoconazole on cyclosporin A-induced inhibition of keratinocyte DNA synthesis.

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.

journal_name

Acta Derm Venereol

authors

Amsellem C,Haftek M,Thivolet J,De Doncker P,Schmitt D

doi

10.2340/0001555574257259

subject

Has Abstract

pub_date

1994-07-01 00:00:00

pages

257-9

issue

4

eissn

0001-5555

issn

1651-2057

journal_volume

74

pub_type

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