Dose-dependent elimination of 8-methoxypsoralen in the mouse

Conference · Sat Mar 01 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5496851

Cheney, P; Pacula, C M; Gerber, N; Mays, D C

8-Methoxypsoralen (8-MOP), a photoactive linear furocoumarin, is effective in the treatment of several diseases, including psoriasis, mycosis fungoides and T-cell leukemia. Recently, a specific extraction procedure for /sup 14/C-8-MOP showed that the elimination of 8-MOP in the rat was dose-dependent. Similar pharmacokinetic studies were undertaken in mice. Purity of /sup 14/C-8-MOP, verified by a four-tube countercurrent distribution using hexane (8 ml) and pH 7.4 phosphate buffer (0.1 M 15 ml) as described by Bush, was >98% and distributed with a partition coefficient of 3.86. Male CD-1 mice were each given an i.p. dose of 10 or 50 mg/kg of /sup 14/C-8-MOP (3.4 ..mu..Ci/mg) sacrificed at timed intervals, homogenized in 150 ml of 0.1 M phosphate buffer (pH 7.4) and a portion (0.8 ml) of the homogenate used to quantify 8-MOP as described above. The elimination half-life measured in the first 45 min was 7.4 min at 10 mg/kg and 95 min at 50 mg/kg. A similar half-life of 9.2 min was measured in mice given an i.v. dose 10 mg/kg of 8-MOP. Explanations of dose-dependent elimination include enzyme saturation, product inhibition or both. Between 58-80% of the administered radioactivity was recovered in the urine within 24 hr. Nine peaks of radioactivity were observed in the urine by HPLC, two of which coeluted with 5,8-dihydroxypsoralen and 6-(7-hydroxy-8-methoxycoumaryl)-acetic acid.

• Research Organization: Ohio State Univ. College of Medicine, Columbus
• OSTI ID: 5496851
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:3
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ANTICOAGULANTS
BIOLOGICAL HALF-LIFE
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
CARBON 14 COMPOUNDS
CHROMATOGRAPHY
CLEARANCE
COUMARINS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
EXCRETION
HEMATOLOGIC AGENTS
HETEROCYCLIC COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MATERIALS
MICE
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PSORALEN
PURIFICATION
RODENTS
SEPARATION PROCESSES
TRACER TECHNIQUES
URINE
VERTEBRATES
WASTES