Pharmacokinetic behaviour of sublingually administered 8-methoxypsoralen for PUVA therapy.

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.

• Authors: S E Shephard, P Langguth, R G Panizzon
• Journal: Photodermatology, photoimmunology & photomedicine (Photodermatol Photoimmunol Photomed) Vol. 17 Issue 1 Pg. 11-21 (Feb 2001) ISSN: 0905-4383 [Print] England
• PMID: 11169171 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Excipients
• Methoxsalen

Topics

• Administration, Sublingual
• Adult
• Aged
• Analysis of Variance
• Excipients
• Female
• Humans
• Male
• Methoxsalen (administration & dosage, pharmacokinetics)
• Middle Aged
• PUVA Therapy
• Psoriasis (drug therapy)