Percutaneous absorption and pharmacokinetics of eflornithine HCl 13.9% cream in women with unwanted facial hair.
This article reports the results of an open-label, multiple-dose study to determine percutaneous absorption and pharmacokinetics of eflornithine following topical treatment with eflornithine HCl 13.9% cream (Vaniqa). Ten women with excessive facial hair were treated with two 0.5 g single doses of [14C]-labeled eflornithine HCl 13.9% (w/w) cream (periods A and C) separated by twice-daily application of 0.5 g unlabeled eflornithine HCl 13.9% cream for 7 days (period B). Analysis of radioactivity excreted in urine and feces indicated that percutaneous absorption was minimal. Comparison with urinary excretion of eflornithine in period A suggested that most of absorbed eflornithine was excreted in urine without being metabolized. Radioactivity was not detectable in blood or plasma, but eflornithine concentrations were measurable, with peak concentrations of 4.96 ng/ml in period A and 10.44 ng/ml in period C. Eflornithine was eliminated from plasma with a mean terminal half-life of 11 hours (first application) and 8 hours (final application). Trough plasma concentrations reached steady state (4.61-5.50 ng/ml) after 4 days of twice-daily topical treatment, and multiple dosing had no apparent effect on disposition kinetics. The low degree of percutaneous absorption and low systemic exposure to eflornithine offer a favorable clinical safety profile of eflornithine HCl 13.9% cream.
Malhotra
B
B
Bristol-Myers Squibb, Princeton, New Jersey 08540, USA.
Noveck
R
R
Behr
D
D
Palmisano
M
M
D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D000518:Eflornithine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005243:Feces / Q000737:chemistry; D005260:Female; D006204:Hair Removal; D006628:Hirsutism / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D012869:Skin Absorption / Q000502:physiology*
D004791:Enzyme Inhibitors; D000518:Eflornithine