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IARC Monographs on the Evaluation of... 1980
Topics: Animals; Chemical Phenomena; Chemistry; Cocarcinogenesis; DNA; Female; Humans; Male; Methoxsalen; Mice; Mutagenicity Tests; Neoplasms, Experimental; Skin Neoplasms; Terminology as Topic; Ultraviolet Rays
PubMed: 6937435
DOI: No ID Found -
Clinical Pharmacokinetics 1986The psoralen derivative methoxsalen and to a lesser extent some other furocoumarin congeners, including bergapten and trioxsalen, have acquired a place in the treatment... (Review)
Review
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.
Topics: 5-Methoxypsoralen; Administration, Oral; Biopharmaceutics; Diet; Furocoumarins; Humans; Intestinal Absorption; Kinetics; Methoxsalen; PUVA Therapy; Protein Binding; Psoriasis; Skin Absorption; Trioxsalen
PubMed: 3512141
DOI: 10.2165/00003088-198611010-00004 -
Journal of the American Academy of... Sep 1986
Topics: Adult; Female; Humans; Methoxsalen
PubMed: 3760281
DOI: 10.1016/s0190-9622(86)80498-4 -
Journal of Pharmaceutical Sciences Apr 1979Significant improvement in the effective bioavailability of methoxsalen was achieved when it was administered to rats and dogs in a solution as compared to a suspension....
Significant improvement in the effective bioavailability of methoxsalen was achieved when it was administered to rats and dogs in a solution as compared to a suspension. Much earlier and higher peak levels were observed for the solution in both animals. The possible impact of these observations on current use of this agent for psoriasis treatment is discussed.
Topics: Administration, Oral; Animals; Biological Availability; Capsules; Chromatography, High Pressure Liquid; Dogs; Injections, Intravenous; Male; Methoxsalen; Models, Biological; Rats; Solutions; Suspensions
PubMed: 438967
DOI: 10.1002/jps.2600680415 -
Journal of the American Academy of... Aug 1979
Topics: Carcinoma, Squamous Cell; Humans; Methoxsalen; Photochemotherapy; Psoriasis; Skin Neoplasms; Ultraviolet Therapy
PubMed: 521514
DOI: 10.1016/s0190-9622(79)80035-3 -
British Medical Journal Jul 1978
Topics: Humans; Methoxsalen; Photochemotherapy; Psoriasis; Ultraviolet Therapy
PubMed: 678788
DOI: No ID Found -
Biomedicine & Pharmacotherapy =... Feb 2022Acetylcholinesterase (AChE) inhibitor is the first choice for the treatment of Alzheimer's disease (AD), but it has some defects, such as dose limitation and... (Review)
Review
Acetylcholinesterase (AChE) inhibitor is the first choice for the treatment of Alzheimer's disease (AD), but it has some defects, such as dose limitation and unsatisfactory long-term treatment effect. Recent studies have shown that butyrylcholinesterase (BuChE) inhibitors or double acetyl and butyryl cholinesterase inhibitors have better curative effects on AD, and the side effects are lower than those of specific AChE inhibitors. Dual target cholinesterase inhibitors have become a new hotspot in the research of anti-AD drugs. Herein, the synthesis and bioactivities of BuChE inhibitors were reviewed.
Topics: Acridines; Alzheimer Disease; Butyrylcholinesterase; Cholinesterase Inhibitors; Humans; Methoxsalen; Structure-Activity Relationship
PubMed: 34953393
DOI: 10.1016/j.biopha.2021.112556 -
Bioorganic & Medicinal Chemistry Letters Feb 2019Linear furocoumarins, also known as psoralens, are clinically useful photo-activated pharmaceuticals employed to address hyperproliferative skin diseases. Seven diverse...
Linear furocoumarins, also known as psoralens, are clinically useful photo-activated pharmaceuticals employed to address hyperproliferative skin diseases. Seven diverse cytotoxic pharmacophores have been synthetically attached to 8-methoxypsoralen via a 5-amino functionality. The resulting unique set of compounds was evaluated for dark and light toxicity against PAM212 keratinocytes in culture.
Topics: Cell Survival; Cells, Cultured; Darkness; Humans; Keratinocytes; Light; Methoxsalen; Photosensitizing Agents; Skin Diseases
PubMed: 30638875
DOI: 10.1016/j.bmcl.2018.12.048 -
Archives of Dermatology Dec 1981
Topics: Humans; Methoxsalen; PUVA Therapy; Photochemotherapy
PubMed: 7316545
DOI: No ID Found -
American Journal of Hospital Pharmacy Jul 1981The effectiveness of methoxsalen and ultraviolet light (PUVA) in treating is reviewed. The use of this therapy, its mechanism of action, pharmacology, pharmacokinetics,... (Review)
Review
The effectiveness of methoxsalen and ultraviolet light (PUVA) in treating is reviewed. The use of this therapy, its mechanism of action, pharmacology, pharmacokinetics, adverse reactions, dosage, and comparison with other forms of therapy, are discussed. Administered orally, methoxsalen in combination with long-range ultraviolet light (UVA) is effective in treating patients with moderate to severe forms of psoriasis. Although the short-term risks associated with PUVA therapy are minimal, the long-term risks of oncogenicity have not been evaluated thoroughly. Common adverse reactions to methoxsalen and UVA are nausea, pruritus, and erythema, but usually they can be managed by minor modifications in the treatment regimen. Methoxsalen and UVA therapy should be reserved for patients with moderate to severe forms of psoriasis that do not respond to other forms of therapy until the long-term risks of oncogenicity are evaluated.
Topics: Humans; Kinetics; Methoxsalen; PUVA Therapy; Photochemotherapy; Psoriasis
PubMed: 7020414
DOI: No ID Found