Loprox (Ciclopirox Topical) - Description and Clinical Pharmacology

FOR DERMATOLOGIC USE ONLY.
NOT FOR USE IN EYES.

Rx Only

DESCRIPTION

LOPROX^® Gel (ciclopirox) 0.77% contains a synthetic antifungal agent, ciclopirox. It is intended for topical dermatologic use only.

Each gram of LOPROX^® Gel contains 7.70 mg of ciclopirox in a gel consisting of Purified Water USP, Isopropyl Alcohol USP, Octyldodecanol NF, Dimethicone Copolyol 190, Carbomer 980, Sodium Hydroxide NF, and Docusate Sodium USP.

LOPROX^® Gel is a white, slightly fluid gel.

The chemical name for ciclopirox is 6-cyclohexyl-1-hydroxy-4-methyl-2(1 H)-pyridinone, with the empirical formula C₁₂H₁₇NO₂ and a molecular weight of 207.27. The CAS Registry Number is [29342-05-0]. The chemical structure is:

CLINICAL PHARMACOLOGY

Mechanism of Action

Ciclopirox acts by chelation of polyvalent cations (Fe³⁺ or Al³⁺) resulting in the inhibition of the metal-dependent enzymes that are responsible for the degradation of peroxides within the fungal cell.

In vitro studies showed that ciclopirox inhibited the formation of 5-lipoxygenase inflammatory mediators (5-HETE and LTB₄) and also inhibited PGE₂ release in a cell culture model. In vivo, ciclopirox inhibited inflammation in an arachidonic acid-induced murine ear edema model. The clinical significance of these findings is unknown.

Pharmacokinetics

A comparative study of the pharmacokinetics of LOPROX^® Gel, and LOPROX^® Cream (ciclopirox olamine) 0.77% in 18 healthy males indicated that systemic absorption of ciclopirox from LOPROX^® Gel was higher than that of LOPROX^® Cream. A 5 gm dose of LOPROX^® Gel produced a mean (±SD) peak serum concentration of 25.02 (±20.6) ng/mL total ciclopirox and 5 gm of LOPROX^® Cream produced 18.62 (±13.56) ng/mL total ciclopirox. Approximately 3% of the applied ciclopirox was excreted in the urine within 48 hours after application, with a renal elimination half-life of about 5.5 hours.

In a study of LOPROX^® Gel, 16 men with moderate to severe tinea cruris applied approximately 15 grams/day of the gel for 14.5 days. The mean (±SD) dose-normalized values of C_max for total ciclopirox in serum were 100 (±42) ng/mL on Day 1 and 238 (±144) ng/mL on Day 15. During the 10 hours after dosing on Day 1, approximately 10% of the administered dose was excreted in the urine.

Microbiology

Ciclopirox is a hydroxypyridinone antifungal agent that inhibits the growth of pathogenic dermatophytes. Ciclopirox has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section:

Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum.