IngentaConnect Dosage plan of a flurbiprofen injection product using inhibition ...

Authors: Ogata, Kenji¹; Takamura, Norito²; Tokunaga, Jin²; Kawai, Keiichi³; Arimori, Kazuhiko⁴; Higuchi, Shun⁵

Source: Journal of Pharmacy and Pharmacology, Volume 60, Number 1, January 2008 , pp. 15-20(6)

Abstract:

Flurbiprofen-axetil (FP-ax), a bolus injection product of a non-steroidal anti-inflammatory drug (NSAID), is a prodrug of flurbiprofen, an NSAID. As flurbiprofen strongly binds to site II of human serum albumin (HSA), the free (unbound) concentration of flurbiprofen after injection of FP-ax is low. We have examined the inhibitory effect of free fatty acid (FFA), a binding inhibitor for site II of HSA, on the binding of flurbiprofen in-vitro and in-vivo by ultrafiltration, to establish an effective dosage of FP-ax. In-vitro, fatty acid mixtures (FAs) inhibited the binding of flurbiprofen to rat serum albumin. The free fraction of flurbiprofen was remarkably increased by FAs in rat serum. In-vivo, FP-ax was injected into a control group (low FFA concentration in serum) and a lipid emulsion group (high FFA concentration in serum). The area under the curve of the free concentration of flurbiprofen during the alpha phase and the distribution volume of the central compartment of flurbiprofen were significantly higher in the lipid emulsion group than the control group (5.0- and 1.2-times, respectively). When FP-ax was administered at high FFA concentration, the free concentration of flurbiprofen and distribution of flurbiprofen to tissues increased transiently. This administration method may be useful for patients with cancer pain, having a potent analgesic effect.

Document Type: Research article

DOI: 10.1211/jpp.60.1.0002

Affiliations: 1: Second Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, 1714-1 Yoshino, Nobeoka, Miyazaki, 882-8508, Japan; Clinical Pharmacokinetics, Division of Clinical Pharmacy, Department of Medico 2: Second Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, 1714-1 Yoshino, Nobeoka, Miyazaki, 882-8508, Japan 3: School of Health Sciences, Faculty of Medical, Kanazawa University, 5-11-80 Kadatsuno, Kanazawa, Ishikawa, 920-0942, Japan 4: Department of Pharmacy, Miyazaki Medical College Hospital, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan 5: Clinical Pharmacokinetics, Division of Clinical Pharmacy, Department of Medico-Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan

Dosage plan of a flurbiprofen injection product using inhibition of protein binding by lipid emulsion in rats