title: Investigation of low levels of plasma valproic acid concentration following simultaneous administration of sodium valproate and rizatriptan benzoate.
abstract: Drug interaction between rizatriptan benzoate, an anti-migraine agent, and sodium valproate (VPA-Na), an anticonvulsant, was studied in rats. When rizatriptan benzoate was administered orally immediately after VPA-Na oral administration, the pharmacokinetic parameters, such as plasma valproic acid (VPA) and area under the plasma concentration-time curve up to 3 h (AUC(0-3)), were significantly decreased compared with those in the control group. However, when rizatriptan benzoate was administered intraperitoneally immediately after VPA-Na orally, these parameters were not changed. In addition, when benzoic acid was administered orally immediately after VPA-Na orally, these were significantly lower compared with the control values. Therefore, it might be possible that VPA transport by monocarboxylate transporter was competitively inhibited by rizatriptan benzoate and thus absorption of VPA was decreased.
authors.affiliation: Department of Hospital Pharmacy, Faculty of Medicine, University of the Ryukyus, 207 Aza Uehara, Nishihara-cho, Okinawa 903-0215, Japan. hokama-ryk@umin.ac.jp
authors.forename: Nobuo
authors.initials: N
authors.lastname: Hokama
authors.forename: Norio
authors.initials: N
authors.lastname: Hobara
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Kameya
authors.forename: Susumu
authors.initials: S
authors.lastname: Ohshiro
authors.forename: Narumi
authors.initials: N
authors.lastname: Hobara
authors.forename: Matao
authors.initials: M
authors.lastname: Sakanashi
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D008297:Male; D027501:Monocarboxylic Acid Transporters; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage*; D014230:Triazoles / Q000008:administration & dosage*; D014363:Tryptamines / Q000008:administration & dosage*; D014635:Valproic Acid / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*
chemical_list: D000927:Anticonvulsants; D027501:Monocarboxylic Acid Transporters; D017366:Serotonin Receptor Agonists; D014230:Triazoles; D014363:Tryptamines; C093622:rizatriptan; D014635:Valproic Acid