PT  - JOURNAL ARTICLE
AU  - Helton, David R.
AU  - Osborne, David W.
AU  - Pierson, Sharon K.
AU  - Buonarati, Michael H.
AU  - Bethem, Robert A.
TI  - Pharmacokinetic Profiles in Rats After Intravenous, Oral, or Dermal Administration of Dapsone
DP  - 2000 Aug 01
TA  - Drug Metabolism and Disposition
PG  - 925--929
VI  - 28
IP  - 8
4099  - http://dmd.aspetjournals.org/content/28/8/925.short
4100  - http://dmd.aspetjournals.org/content/28/8/925.full
SO  - Drug Metab Dispos2000 Aug 01; 28
AB  - Dapsone is a potent anti-inflammatory and antibacterial agent that has been used extensively in the oral treatment of leprosy and dermatitis herpetiformis. This study compared the pharmacokinetic profile of dapsone in rats given a single oral or i.v. 12 mg/kg dose (n = 8/group) or a single dermal application of 12 or 60 mg/kg (n = 12/group) in an aqueous gel application medium containing 10 or 25% diethylene glycol monoethyl ether (DGME). Blood samples (200 μl) were collected via tail vein from each rat and pooled at intervals up to the 24-h period. A terminal blood sample was collected by cardiac puncture from each animal. Plasma concentrations of dapsone were determined by liquid chromatography atmospheric pressure ionization tandem mass spectroscopy. There was no treatment-related overt toxicity observed in any of the animals. Peak levels were reached 1 h after oral dosing (4890 ng/ml), and 6 to 8 h after dermal application, withCmax values of 1.62, 5.56, and 12.8 ng/ml, for 12 mg/kg at 10 or 25% DGME, and for 60 mg/kg at 25% DGME, respectively. Bioavailability was calculated at 78% after oral dosing and <1% after dermal application. Apparent elimination half-lives (t1/2)s were similar after i.v. and oral dosing. Both the calculated area under the plasma concentration versus time curve up to 24 h andCmax values were 3- to 4-fold higher in the dermal application group administered 12 mg/kg dapsone in 25 versus 10% DGME gel, whereas the calculated area under the plasma concentration versus time curve up to 24 h andCmax values for the 60 mg/kg group were only 3.3- and 2.3-fold greater than those obtained after application of 12 mg/kg in 25% DGME. These results show that both systemic exposure and peak plasma concentrations of dapsone are minimized by dermal versus oral administration of the compound. The American Society for Pharmacology and Experimental Therapeutics