Dietary influences on 8-MOP plasma levels in PUVA patients with psoriasis

Roelandts, Rik; Boven, Maurits Van; Deheyn, T; Stichele, Geert Vander; Degreef, Hugo; Daenens, Paul

doi:10.1111/j.1365-2133.1981.tb00801.x

Cited by 24 publications

(9 citation statements)

References 5 publications

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“…The differences between these two studies are probably due to the differences in drug formulations and in the composition of the standard diet. Roelandts et al (1981a) found that a lowfat meal did not affect the absorption phase of a plasma concentration-time curve whereas a highfat breakfast caused a significant decrease in methoxsalen concentrations at the time of UV A irradiation. Due to the short sampling time in this study, which was performed in 8 patients, Cmax, tmax and AUC could not be calculated.…”

Section: Influence Of Foodmentioning

confidence: 96%

Clinical Pharmacokinetics of Methoxsalen and Other Psoralens

Wolff

Thomas

1986

Clinical Pharmacokinetics

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The psoralen derivative methoxsalen and to a lesser extent some other furocoumarin congeners, including bergapten and trioxsalen, have acquired a place in the treatment of psoriasis and other dermatoses. They are inactive after oral or topical administration unless combined with irradiation with long-wave ultraviolet light (UVA). This combination is referred to as photochemotherapy or PUVA (psoralen plus UVA). Usually a standard dose of methoxsalen (0.5 to 0.7 mg/kg) is given 2 hours prior to irradiation, and the light dose is assessed individually. Differences in response are often due to the unpredictable pharmacokinetic behaviour of the drug. Reversed-phase high-performance liquid chromatography is the method of choice for determining methoxsalen concentrations in body fluids, but gas chromatography with electron capture detection and thin-layer chromatography with fluorescence densitometry also give favourable results. The absorption of methoxsalen, and hence clinical response, is affected by concomitant food ingestion and by differences in drug formulation. A liquid preparation in soft gelatin capsules or a microenema give higher and more rapidly appearing maximum serum concentrations (Cmax) than crystalline methoxsalen in tablets or capsules. With a standard dose of tablets, Cmax is in the range of 50 to 250 micrograms/L and appears between 1 and 2 hours after ingestion. The drug has a high, but variable, intrinsic metabolic clearance and is almost completely metabolised. Serum elimination half-life is in the order of 0.5 to 2 hours. There is a large interpatient variability in the clearance of methoxsalen (40 to 650 L/h); the relative distribution volume ranges between 1 and 9 L/kg. Concentrations in suction blister fluid (sbf) are approximately one-third of Cmax in serum and remain relatively constant as long as the plasma concentration exceeds the suction blister fluid level. Individuals with a high methoxsalen clearance and low Cmax usually show less biological sensitivity to PUVA (in terms of minimal phototoxic dose of UVA) than low-clearance patients and frequently a less favourable clinical response. Hence Cmax can be used for the purpose of therapeutic drug monitoring and, in practice, this may be determined by measuring serum concentrations at least at 1, 2, and 3 hours after ingestion. Bergapten is somewhat less active than methoxsalen but has similar pharmacokinetic characteristics. The bioavailability of trioxsalen is poor after oral intake and this drug is mainly administered topically.

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Section: Influence Of Foodmentioning

confidence: 96%

Clinical Pharmacokinetics of Methoxsalen and Other Psoralens

Wolff

Thomas

1986

Clinical Pharmacokinetics

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“…Several authors [1,6] have clearly demonstrated that the absorption of 8-MOP varies significantly according to the composition of the meal which accompanies the ingestion of the drug.…”

Section: Commentsmentioning

confidence: 99%

Comparison between Plasma Levels of 8-Methoxypsoralen and Skin Photosensitivity: The Interest of Pharmacokinetic Studies during Photochemotherapy of Psoriasis

Béani¹,

Sarrazin²,

Amblard³

et al. 1983

Dermatology

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“…Concomitant intake of food can affect both the rate and the extent of drug absorption [11][12][13], and consequently it might be important to standardize the Correspondence to: H. Ehrsson, Karolinska Pharmacy, Box 160, S-17176 Stockholm, Sweden food intake in relation to the administration of the psoralens. The influence of food on the pharmacokinetics of 8-MOP has been studied [14][15][16]. However, no general conclusions can be drawn from these studies with regard to the food effect, since different drug formulations and diet compositions have been used.…”

mentioning

confidence: 99%

Food-induced increase in bioavailability of 5-methoxypsoralen

Ehrsson¹,

Wallin²,

Ros

et al. 1994

Eur J Clin Pharmacol

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5-Methoxypsoralen (5-MOP) in combination with ultraviolet light exposure is used for the treatment of psoriasis. The effect of food on the pharmacokinetics of 5-MOP was evaluated in a randomized, crossover study in nine healthy subjects. Each subject received the tablets with a standardized breakfast or under fasting conditions. The food had a dramatic effect on the bioavailability of 5-MOP. Five of the subjects showed no measurable quantities (detection limit of the analytical technique 1 ng.ml-1) of 5-MOP when the drug was given under fasting conditions. However, plasma peak concentration within the range 37-144 ng.ml-1 (median 102 ng.ml-1) was measured when the drug was taken with food. The time for the plasma peak concentration was within the range 2.0-5.1 h (median 3.0 h) under non-fasting conditions. The elimination half-life was within the range 1.4-2.7 h (median 1.9 h). We conclude that it is imperative that 5-MOP tablets are administered together with food.

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Dietary influences on 8-MOP plasma levels in PUVA patients with psoriasis

Cited by 24 publications

References 5 publications

Clinical Pharmacokinetics of Methoxsalen and Other Psoralens

Clinical Pharmacokinetics of Methoxsalen and Other Psoralens

Comparison between Plasma Levels of 8-Methoxypsoralen and Skin Photosensitivity: The Interest of Pharmacokinetic Studies during Photochemotherapy of Psoriasis

Food-induced increase in bioavailability of 5-methoxypsoralen

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