Microenema of 8-methoxypsoralen in photochemotherapy of psoriasis

Siddiqui, A. H.; Stolk, L. M. L.; Vinninghe, H. R. Korthals Altes-Levij van; Kammeijer, A.; Cormane, R. H.

doi:10.1007/bf00409249

Cited by 7 publications

(2 citation statements)

References 13 publications

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“…It has therefore been suggested to have a high degree of first-pass metabolism Schmid et al 1980b;Stolk 1982). This phenomenon may partly contribute to the huge interpatient variation seen in several studies.…”

Section: Metabolismmentioning

confidence: 96%

“…In search of a method of administration without the disadvantages of oral and topical application, Stolk et al (1981a) and Siddiqui et al (1982Siddiqui et al ( ,1984 developed a method for rectal administration of the drug. In 7 volunteers it was shown that high peak serum concentrations of methoxsalen were reached soon after administration (mean tmax = 0.7 ± 0.3h).…”

Section: Rectal Absorptionmentioning

confidence: 99%

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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: Metabolismmentioning

confidence: 96%