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Pharmacokinetic behaviour of sublingually administered 8-methoxypsoralen for PUVA therapy

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Abstract:

Background:

Conventional oral PUVA therapy is hampered by large inter- and intraindividual variations in the bioavailability of 8-methoxypsoralen (8-MOP), caused by its low solubility in the gastrointestinal juices and large interindividual differences in hepatic metabolism rate (hepatic first pass). Aims:

New galenic formulations of 8-MOP based on solid dispersions, suspensions, and saturated solutions containing penetration enhancers were developed for sublingual administration, a drug delivery route which avoids the hepatic first pass metabolism. Methods:

Solubility properties of 8-MOP were tested in 22 potential penetration enhancers and solubilizers. Following preliminary in vivo tests of 13 sublingual 8-MOP formulations, five were administered to groups of volunteers at a nominal dose of 0.6 mg/kg body weight: two solid dispersions based on PEG 1540 (with and without Xylitol); a solution in Labrasol® (glyceryl and PEG-8 caprylate/caprate), PEG 400, Transcutol® (ethoxydiglycol) (1:1:1); a micronized suspension in sorbitol, water, ethanol, propylene glycol (ca. 3:1:1:5 w/v); and Oxsoralen® capsules. Pharmacokinetic behaviour of 8-MOP was examined in serum; samples were analysed by HPLC. Photosensitivity was measured in seven subjects. Results:

The peak of maximum 8-MOP concentration in blood was sharp, rapid and reproducible: tmax of 8-MOP in blood averaged 23±3 min, independent of the particular formulation. Cmax was higher when 8-MOP was presented in dissolved form (solution and capsule formulations, 85±29 and 85±35 ng/ml, respectively) and lowest with the suspension (42±15 ng/ml). Photosensitivity peaked reproducibly at 45 min. post dosing. Conclusions:

Sublingual PUVA therapy is suitable for patients with skin types I and II, in particular patients who are less suitable candidates for standard PUVA therapy (due to hepatic, renal, or cardiac insufficiency) or who have experienced side effects with standard PUVA.

Keywords: absorption; administration route; bioavailability; galenic formulation; hepatic first pass

Document Type: Original Article

DOI: http://dx.doi.org/10.1034/j.1600-0781.2001.017001011.x

Affiliations: Department of Applied Biosciences, Swiss Federal Institute of Technology, Zürich, Switzerland

Publication date: February 1, 2001

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