Evaluation of Lipid Emulsion-Mediated Sequestration and Redistribution of the Highly Lipophilic Carbamazepine in the Plasma of Rats

Yıl 2024, , 1 - 7, 31.03.2024

Merve Ekşioğlu , Deniz Algedik Gürsoy , Engin Sümer , Fadime Canbolat , Sezgin Sarıkaya

https://doi.org/10.54996/anatolianjem.1354717

Öz

Aim: The idea that intravenous lipid emulsion (ILE) may serve as a "reservoir" for lipophilic drugs has emerged in research as an intravascular "lipid sink" effect. Carbamazepine (CBZ) is a widely used anticonvulsant. This compound has a neutral and highly lipophilic structure and can easily cross body membranes. In this study, our hypothesis focused on the potential efficacy of ILE in modulating blood carbamazepine concentrations.

Material and Methods: 22 adult Sprague-Dawley rats were divided into four groups. All groups received CBZ at a dose of 20 mg/kg orogastrically. The first group was the control group. In the second group (activated charcoal group), activated charcoal (AC) was administered orogastrically at a dose of 1 g/kg five minutes after orogastric administration of carbamazepine. The third group (lipid group) received ILE at a dose of 3 ml/kg/min at the fifth minute. The fourth group was the saline group, in which 16 ml/kg of 0.9% NaCl was infused at the fifth minute. Blood samples of 0.5 ml were collected at 0, 4, 8, and 24 hours. Plasma was separated by centrifugation (4000 rpm, 10 minutes) and stored at -80oC for determination of CBZ concentrations. An Agilent 6410B HP-1200 LC series (USA) liquid chromatography system was used for analysis. Quantitative analysis was performed in the multiple reaction mode with electrospray positive ionization (ES+).

Results: At the 8th hour of orogastric CBZ administration, CBZ concentration was significantly lower in the activated charcoal group than in the lipid and saline groups (p: 0.021; p: 0.023; p<0.05, respectively). There was no significant difference in CBZ concentrations between the other groups at 8 hours (p>0.05). In the lipid group, the increase in CBZ plasma concentrations was statistically significant at 4 and 8 hours compared to 0 hours (p: 0.005; p: 0.005, respectively).

Conclusion: In the lipid group, plasma CBZ concentrations increased at 4 and 8 hours in plasma samples from which lipids were separated by differential centrifugation. In the lipid group, no effects favoring drug-lipid sequestration on the plasma distribution of CBZ were observed.

Anahtar Kelimeler

Intralipid, lipid emulsion, carbamazepine, liquid chromatography, lipid sink

Etik Beyan

The study (decision number: 634, approval date: 22.12.2017) was initiated following the approval of the Ethics Committee of the Local Ethics Committee for Animal Experiments at Yeditepe University. The research was conducted at the Laboratory for Experimental Animal Research at the Faculty of Medicine, Yeditepe University, Istanbul, Turkey. The study followed all relevant international, national, and institutional guidelines for the appropriate care and use of animals in research.

Proje Numarası

634

Teşekkür

We are deeply grateful to all those who have contributed to the success of this project. We would like to thank Ahmet Aydın PhD for his invaluable input and support throughout the research process. Their insights and expertise were instrumental in shaping the direction of this project.

Yüksek Lipofilik Karbamazepinin Sıçan Plazmasında Lipid Emülsiyonu Aracılı Sekestrasyonu ve Yeniden Dağılımının Değerlendirilmesi

Öz

Amaç: İntravenöz lipid emülsiyonunun (ILE) lipofilik ilaçlar için bir "rezervuar" görevi görebileceği fikri, intravasküler "lipid sink" etkisi olarak araştırmalarda ortaya çıkmıştır. Karbamazepin (CBZ) yaygın olarak kullanılan bir antikonvülzandır. Bu bileşik nötral ve oldukça lipofilik bir yapıya sahiptir ve vücut membranlarını kolayca geçebilir. Bu çalışmada hipotezimiz, ILE'nin kan karbamazepin konsantrasyonlarını modüle etmedeki potansiyel etkinliğine odaklanmıştır.

Gereç ve Yöntemler: 22 yetişkin Sprague-Dawley sıçan dört gruba ayrıldı. Tüm gruplara 20 mg/kg dozunda CBZ orogastrik olarak verildi. Birinci grup kontrol grubuydu. İkinci grupta (aktif kömür grubu), karbamazepinin orogastrik uygulamasından beş dakika sonra aktif kömür (AC) 1 g/kg dozunda orogastrik olarak uygulandı. Üçüncü gruba (lipid grubu) beşinci dakikada 3 ml/kg/dk dozunda ILE verildi. Dördüncü grup, beşinci dakikada 16 ml/kg %0,9 NaCl infüze edilen salin grubuydu. 0, 4, 8 ve 24. saatlerde 0,5 ml kan örnekleri toplandı. Plazma santrifüj (4000 rpm, 10 dakika) ile ayrıldı ve CBZ konsantrasyonlarının belirlenmesi için -80oC'de saklandı. Analiz için bir Agilent 6410B HP-1200 LC serisi (ABD) sıvı kromatografi sistemi kullanıldı. Kantitatif analiz elektrosprey pozitif iyonizasyon (ES+) ile çoklu reaksiyon modunda gerçekleştirildi.

Bulgular: Orogastrik CBZ uygulamasının 8. saatinde, CBZ konsantrasyonu aktif kömür grubunda lipid ve salin gruplarına göre anlamlı derecede düşüktü (sırasıyla p: 0.021; p: 0.023; p<0.05). Diğer gruplar arasında 8. saatte CBZ konsantrasyonları açısından anlamlı bir fark bulunmadı (p>0.05). Lipid grubunda, CBZ plazma konsantrasyonlarındaki artış başlangıca kıyasla 4 ve 8. saatlerde istatistiksel olarak anlamlıydı (sırasıyla p: 0.005; p: 0.005).

Sonuç: Lipid grubunda, lipidlerin diferansiyel santrifüjleme ile ayrıldığı plazma örneklerinde plazma CBZ konsantrasyonları 4 ve 8. saatlerde artmıştır. Lipid grubunda, CBZ'nin plazma dağılımı üzerinde ilaç-lipid sekestrasyonunu destekleyen herhangi bir etki gözlenmedi.

Anahtar Kelimeler

İntralipid, lipid emülsiyonu, karbamazepin, sıvı kromatografisi, lipid sink

Proje Numarası

634

Kaynakça

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