Binding of primaquine to epidermal membranes and keratin.

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Heard CM, Monk BV, Modley AJ

Binding of primaquine to epidermal membranes and keratin.

Int J Pharm. 2003 May 12;257(1-2):237-44.

PubMed ID

12711178 [ View in PubMed

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Abstract

The localisation of primaquine was studied within epidermal membranes following the application of a topical dose. A depth profile was constructed by tape-stripping human epidermis following permeation of a 70 mgml(-1) solution of primaquine in Miglyol 840. Comparative binding studies of primaquine were carried out on isolated human stratum corneum and whole epidermis, using normal and delipidised tissue. An additional study was undertaken using bovine keratin powder as a model of human keratin. The depth profile showed that primaquine decreased with depth and decreasing keratin content, and the total primaquine recovered (15.5 mgcm(-2)) was 300 x the amount of extractable lipid. Binding to delipidised skin was saturable, whereas binding to normal skin was unsaturable, reflecting the high miscibility of drug in the lipid domains as opposed to a finite, but large number of binding sites on the corneocytes. Binding was greater for stratum corneum than stratum corneum plus viable epidermis, probably due to greater accessibility of corneocytes keratin. Binding was dose dependent, although binding to delipidised skin was far greater than to normal skin, demonstrating that primaquine had an affinity for lipoidal regions and an even higher affinity for the proteinaceous domains of the stratum corneum. This was supported by high saturable levels of primaquine binding to bovine horn keratin. The results indicated extensive binding to corneocyte keratin has a significant effect on reservoir formation and the permeability of primaquine across human skin. It is speculated that the large amount of keratin presented at the skin surface may be an evolutionary protective process for the sequestration of ingressing molecules.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Primaquine	Keratin, type II cytoskeletal 7	Protein	Humans	Unknown	Other/unknown	Details