[PMID]: | 22983645 |
[Au] Autor: | Ochi M; Inoue R; Yamauchi Y; Yamada S; Onoue S |
[Ad] Endereço: | Department of Pharmacokinetics and Pharmacodynamics School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan. |
[Ti] Título: | Development of meloxicam salts with improved dissolution and pharmacokinetic behaviors in rats with impaired gastric motility. |
[So] Source: | Pharm Res;30(2):377-86, 2013 Feb. |
[Is] ISSN: | 1573-904X |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | PURPOSE: Because of its poor solubility in acidic solution, oral absorption and efficacy of meloxicam (MEL) may be reduced in severe pain patients with impaired gastric motility. The present study aimed to develop salt forms to overcome these drawbacks. METHOD: Upon MEL salt screening with eight counterions, five MEL salts were obtained. The physicochemical properties of these MEL salts were characterized with a focus on morphology, crystallinity, thermal behavior, dissolution, and chemical/photo-stability. Pharmacokinetic profiling of an orally administered MEL salt was also carried out in both normal rats and rats treated with propantheline for the suppression of gastric motility. RESULTS: Dissolution behaviors for all obtained MEL salts were markedly better than that of crystalline MEL; in particular, the initial dissolution rate of arginine MEL dihydrate (MEL/Arg) was ca. 14-fold higher than that of crystalline MEL. MEL/Arg was found to be chemically and physically stable. There was ca. 18-fold reduction of AUC(0-4) for orally dosed crystalline MEL (1.0 mg-MEL/kg) in propantheline-treated rats compared with that in normal rats. In contrast, there was only a ca. 3-fold difference in AUC(0-4) between normal and propantheline-treated rats after oral administration of MEL/Arg (1.0 mg-MEL/kg). CONCLUSION: From these findings, MEL/Arg may provide improved oral absorption in severe pain patients. |
[Mh] Termos MeSH primário: |
Anti-Inflamatórios não Esteroides/administração & dosagem Anti-Inflamatórios não Esteroides/farmacocinética Motilidade Gastrointestinal Veículos Farmacêuticos/química Sais/química Tiazinas/administração & dosagem Tiazinas/farmacocinética Tiazóis/administração & dosagem Tiazóis/farmacocinética
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[Mh] Termos MeSH secundário: |
Administração Oral Animais Anti-Inflamatórios não Esteroides/sangue Área Sob a Curva Arginina/química Motilidade Gastrointestinal/efeitos dos fármacos Masculino Antagonistas Muscarínicos/farmacologia Propantelina/farmacologia Ratos Ratos Sprague-Dawley Solubilidade Tiazinas/sangue Tiazóis/sangue
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Muscarinic Antagonists); 0 (Pharmaceutical Vehicles); 0 (Salts); 0 (Thiazines); 0 (Thiazoles); 1306V2B0Q8 (Propantheline); 94ZLA3W45F (Arginine); VG2QF83CGL (meloxicam) |
[Em] Mês de entrada: | 1307 |
[Cu] Atualização por classe: | 171031 |
[Lr] Data última revisão:
| 171031 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 120918 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1007/s11095-012-0878-2 |
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