Problems with Commercial Formulations of 8-Methoxypsoralen

Monbaliu, Johan; Bogaert, Marcus; Bersaques, J. De; Hindryckx, P.

doi:10.1159/000250217

Cited by 5 publications

(3 citation statements)

References 8 publications

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“…Stolk et al (1980) were the first to demonstrate that the area under the serum concentration-time curve (AUCo_4h) could be significantly increased by administering methoxsalen as an aqueous solution instead of as a powder in a gelatin capsule. Several authors have confirmed this observation, namely that administration of methoxsalen in soft gelatin capsules containing the drug in solution leads to higher serum concentrations than micronised powder in hard gelatin capsules or in tablets (Honigsmann et al 1982;Langner & Wolska 1981;Monbaliu et al 1981;Nitsche et al 1981).…”

Section: Fundamental Pharmacokinetic Propertiesmentioning

confidence: 89%

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: Fundamental Pharmacokinetic Propertiesmentioning

confidence: 89%

Clinical Pharmacokinetics of Methoxsalen and Other Psoralens

Wolff

Thomas

1986

Clinical Pharmacokinetics

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“…Oral crystalline 8-MOP in tablet (27,28) crystalline 8-MOP in capsule (29)(30)(31) solution, aqueous (28,32) solution, in 20% aqueous ethanol (31) dissolved, in oil-in-water emulsion (30) micronized 8-MOP in tablet (21) micronized 8-MOP in hard gelatin capsule (30,(32)(33)(34)(35)) dissolved 8-MOP in soft gelatin capsule (29,31,(33)(34)(35) Topical aqueous bath (36)(37)(38) bathing suit soaked in 8-MOP aqueous solution (39) solution in isopropanol:water (40,41) aqueous gel (propylene glycol 10%, carbomer 934P 1%) (42) aqueous emulsion (7% 1,2-propylene glycol) (41) hydrophilic polyethylene glycol ointment (43) oil in water emulsion (43,44) oil and emulgator (Eutanol G) (41) solution in ethanol:acetone:propylene glycol 7:2:1 (45) oil solution (olive oil) (41) solution in hydrophilic petrolatum, mineral oil and wax (40) hydrophobic water in oil emulsion (43) cream (46) vaseline ointment (43) Rectal microenema (35,47) suppository (48,49) i.v. dissolved in isotonic saline solution (50) each individual patient and adjusting the 8-MOP dose and timing of the UVA dose accordingly.…”

Section: Route Of Administration Galenic Form Referencesmentioning

confidence: 99%

Pharmacokinetic behaviour of sublingually administered 8‐methoxypsoralen for PUVA therapy

Shephard

Langguth

Panizzon

2001

Photoderm Photoimm Photomed

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“…Le 8-MOP a été administré à jeun sous forme de solution [3], à trois reprises, aux doses resectives de 0,6, 0,45 et 0,3 mg/kg. Le p-8-MOP est déterminé par chromatographie en phase liquide sous haute pression [4] [6] 0,768 10,5 l/D PM /p-8-M O P [2] 0,691 18,1 1/DPM /log p-8-MOP [6] 0,738 15,7 log DPM/log p-8-MOP x log 1/DPM /log p-8-MOP ^0,764 13,4…”

Section: Méthodesunclassified