Reversible binding of 5- and 8-methoxypsoralen to human serum proteins (albumin) and to epidermis in vitro

Artuc, Metin; Stuettgen, G; Schalla, W.; Schaefer, H.; Gazith, J.

doi:10.1111/j.1365-2133.1979.tb05645.x

Cited by 43 publications

(17 citation statements)

References 9 publications

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“…These rsults agree with those of Artuc et al [12] and Veronese et al [13] concerning the major role of HSA in 5-MOP plasma binding. Artuc et al [12] found an HSA-binding per centage of 98%, however they used a high concentration of HSA (900 pmol/1) with a long time of dialysis.…”

Section: Discussionsupporting

confidence: 83%

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Binding of 5-Methoxypsoralen to Blood Fractions

Muret

Makki

Urien

et al. 1993

Skin Pharmacol Physiol

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The binding of 5-methoxypsoralen (5-MOP) to human serum and blood fractions was studied by equilibrium dialysis associated to high-performance liquid chromatography. 5-MOP serum binding was 95% and kept constant in the range of therapeutic concentrations. Albumin was the main binding protein with one class of binding sites (n = 2.05) and with a moderate affinity constant (K_a = 10,270 M^-1). Free fatty acids (FFA) enhanced 5-MOP binding to albumin. Binding to other proteins, α₁-acid glycoprotein, gamma-globulins and lipoproteins (LDL, HDL, VLDL) also occurred, but was negligible. 5-MOP bound to red blood cells (RBCs) with a binding index (ratio of intra- to extra-globular 5-MOP concentrations) of 3.84 and 1.48 in buffer and plasma, respectively. 5-MOP distribution in blood was simulated. The free fraction of 5-MOP in blood could be increased in hypoalbuminemia, unchanged in acute inflammation, and decreased by FFA.

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Section: Discussionsupporting

confidence: 83%

“…Artuc et al [12] found an HSA-binding per centage of 98%, however they used a high concentration of HSA (900 pmol/1) with a long time of dialysis. Veronese et al [13] found a lower binding percentage (91 %), but they used a lower HSA concentration (450 pmol/1).…”

Section: Discussionmentioning

confidence: 99%

Binding of 5-Methoxypsoralen to Blood Fractions

Muret

Makki

Urien

et al. 1993

Skin Pharmacol Physiol

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“…This is in good agreement with the data of Busch et al (1978) who found serum protein binding to be 88 to 91 %, using 14C_ labelled methoxsalen and equilibrium dialysis. Artuc et al (1979) found a slightly lower percentage (75 to 80%) of protein binding of methoxsalen. Veronese et al (1979) claimed that methoxsalen is bound specifically to the benzodiazepine binding site of albumin, but this could not be confirmed by Bevilacqua et al (1981) who demonstrated that the drug could be displaced from its binding sites by a number of drugs, e.g.…”

Section: Serum Protein Bindingmentioning

confidence: 92%

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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“…The association constants with human serum albumin are similar to those with DNA [4,130] Triplet states of several psoralens are effectively quenched by aromatic amino acids, most notably Trp [12]. However, no chemical reaction has been observed in the absence of oxygen.…”

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confidence: 99%

Dye Binding and Photodynamic Action

Amagasa

1981

Photochem & Photobiology

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A variety of natural and synthetic compounds can act as effective photosensitizers in biological systems, including psoralens, flavins, porphyrins, acridines, phenothiazines, xanthenes, quinones, polyenes, haloaromatics and inorganic ions. These, in the presence of light and oxygen, inactivate and modify the integrity of important biomolecules and cellular structures, leading to cell death, mutation and other special function losses [70,118,119]. Many photosensitizers can act as mediators of photodynamic and non‐photodynamic reactions, depending on the experimental conditions. Although a great variety of photosensitized reactions may occur with different sensitizers and substrates, they can be classified into two types of reaction mechanisms, that is, Type I (radical) and Type II (singlet oxygen; 1O2) mechanisms. Type I and Type II reactions for important biomolecules have recently been reviewed [27, 119].

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Reversible binding of 5- and 8-methoxypsoralen to human serum proteins (albumin) and to epidermis in vitro

Cited by 43 publications

References 9 publications

Binding of 5-Methoxypsoralen to Blood Fractions

Binding of 5-Methoxypsoralen to Blood Fractions

Clinical Pharmacokinetics of Methoxsalen and Other Psoralens

Dye Binding and Photodynamic Action

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