Studies on 8-methoxypsoralen tolbutamide interactions in vitro and in vivo.
The present study aimed at characterizing the influence of tolbutamide on the distribution of 8-methoxypsoralen (8-MOP) in mouse serum and organs. Experiments performed in vitro clearly showed that tolbutamide causes competitive displacement of 8-MOP from its binding sites on human serum albumin. Similarly, the amount of labelled compound(s) bound in serum after oral administration of 3H-8-MOP to mice was significantly reduced when tolbutamide was given by the same route. The quantitative distribution of radioactivity from 3H-8-MOP in mouse tissues varied according to organ (liver, intestine, skin, etc.,), and was maximum in the organs of elimination. In all the organs studied, the administration of tolbutamide 2 hours after that of 3H-8-MOP caused a dose-dependent reduction of the radioactive compound(s) present in tissues, suggesting that tolbutamide may accelerate the excretion of 8-MOP and/or its metabolites from the body.
Dipartimento di Scienze Farmaceutiche, Università di Padova, Italy.
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Bevilacqua
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Baccichetti
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RM
Gaion
D000818:Animals; D003956:Dialysis; D004121:Dimethyl Sulfoxide; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005243:Feces / Q000737:chemistry; D008730:Methoxsalen / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D012709:Serum Albumin / Q000378:metabolism; D014044:Tolbutamide / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
D012709:Serum Albumin; D014044:Tolbutamide; D008730:Methoxsalen; D004121:Dimethyl Sulfoxide