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Sodium citrate buffer improves pazopanib solubility and absorption in gastric acid-suppressed rat model.
Muhammad, Huda Jassim; Shimada, Tsutomu; Fujita, Arimi; Sai, Yoshimichi.
Afiliación
  • Muhammad HJ; Department of Clinical Pharmacokinetics, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan; Department of Clinical Pharmacy, College of Pharmacy, Karbala University, Karbala, 56001, Iraq. Electronic address: huda.j.alhasnawi@gmail.com.
  • Shimada T; Department of Clinical Pharmacokinetics, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan; Department of Hospital Pharmacy, University Hospital, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan. Electronic address: t-shimada@staf
  • Fujita A; Department of Clinical Pharmacokinetics, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan; Department of Hospital Pharmacy, University Hospital, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan. Electronic address: a-ueda@staff.k
  • Sai Y; Department of Clinical Pharmacokinetics, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan; Department of Hospital Pharmacy, University Hospital, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan. Electronic address: sai-ys@staff.k
Drug Metab Pharmacokinet ; 55: 100995, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38447327
ABSTRACT
Pazopanib exhibits pH-dependent solubility and its absorption depends primarily on the stomach pH. Significant decrease of pazopanib absorption by coadministration with proton pump inhibitors in clinical situation need to be overcome. Thus, the purpose of this study is firstly to investigate the effect of acidic beverages and sodium citrate buffer on the solubility of pazopanib and secondly to examine the effect of sodium citrate buffer on pazopanib absorption in a rat model with esomeprazole-mediated gastric acid suppression. Pazopanib solubility decreased with increasing pH of sodium citrate buffer in vitro. Interestingly, its solubility in some acidic beverages was significantly lower than that in sodium citrate buffer of the same pH. The AUC0-24h of pazopanib administered in tap water to rats treated with esomeprazole (ESP rats) was 66 % lower than that in the control rats treated with saline. However, AUC0-24h was 4.8 times higher in ESP rats that received pazopanib with sodium citrate buffer (pH 2.3) compared to ESP rats that received pazopanib with tap water. Our results indicate that the drug-drug interactions between pazopanib and proton pump inhibitors can be overcome, at least in part, by suspending pazopanib in sodium citrate buffer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirimidinas / Sulfonamidas / Inhibidores de la Bomba de Protones / Esomeprazol / Indazoles Límite: Animals Idioma: En Revista: Drug Metab Pharmacokinet Asunto de la revista: FARMACOLOGIA / METABOLISMO Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirimidinas / Sulfonamidas / Inhibidores de la Bomba de Protones / Esomeprazol / Indazoles Límite: Animals Idioma: En Revista: Drug Metab Pharmacokinet Asunto de la revista: FARMACOLOGIA / METABOLISMO Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido