Klorpromazin Hidroklorürün İnsan Eritrositleri Tarafından Tutulumunun in Vitro Karakterizasyonu: Konsantrasyon ve Hematokritin Etkisi

Year 2010, Issue: 2, 157 - 170, 01.06.2010

Emel Öykü Cetin Selma Sahin

Abstract

Eritrositlerin hızla penetre olan maddeler için herhangi bir bariyer etkisi oluşturması beklenmese de eritrositlerle yavaş dengelenen ve/veya aşırı partisyon gösteren bileşiklerin dağılımı ve eliminasyonu üzerinde önemli etkileri olabilir. Klorpromazin hidroklorür CPZ , eritrosit tutulumu üzerine konsantrasyon ve hematokritin etkisini incelemek amacıyla model ilaç olarak seçilmiştir. Hematokrit değerleri 4.06-7.76x106 hücre/ mL olan eritrosit süspansiyonu ve tam kan değişik CPZ konsantrasyonları 5, 7.5, 10, 15 μg/mL ile inkübe edilmiştir. Eritrosit membranı süspansiyonu ve hemolizat da CPZ 5, 15 μg/mL ile inkübe edilmiştir. Tampon fazındaki CPZ’nin absorbansı 30 dakika süreyle 2.5 dakika aralıklarla otomatik olarak ölçülmüştür. Ortalama dengeye ulaşma zamanı ve eğri altında kalan alan AUC tampon konsantrasyon zaman profillerinden tayin edilirken ilaç tutulum derecesi ve eritrosit membranından permeasyon katsayısı eritrosit konsantrasyon zaman profillerinden hesaplanmıştır. Bütün şartlarda tampon ve eritrositler arasındaki dengeye 15 dakika içinde erişilmiş ve AUC ile CPZ dozu arasında lineer bir korelasyon bulunmuştur. Eritrosit süspansiyonu kullanıldığında tutulum hem konsantrasyon hem de hematokritten etkilenmiştir. Buna karşılık tam kan süspansiyonu kullanıldığında CPZ tutulumu %34 civarı ilaç konsantrasyonundan etkilenmemektedir. Ek olarak bütün koşullarda CPZ için permeasyon katsayısı 0.34-6.75x10-6 cm/s sınırları arasındadır.

Keywords

Klorpromazin Hidroklorür, Eritrosit, Hematokrit, Permeasyon Katsayısı

In Vitro Characterization of Chlorpromazine Hydrochloride Uptake by Human Erythrocytes: Effect of Concentration and Hematocrit

Abstract

Although erythrocytes are not expected to constitute any barrier effect for rapidly penetrating substances, they may have profound effects on the distribution and elimination of compounds that slowly equilibrates and/or extensively partition into erythrocytes. Chlorpromazine hydrochloride CPZ was chosen as a model compound to investigate the effect of concentration and hematocrit on erythrocyte uptake. Suspensions of erythrocyte with hematocrit values of 4.06-7.76x106 cell/mL and whole blood were incubated with CPZ solutions 5, 7.5, 10, 15 μg/mL . Suspensions of erythrocyte membranes and hemolysates were also incubated with CPZ 5, 15 μg/mL . Absorbance of CPZ in buffer phase was automatically measured at 2.5 min. intervals for 30 min. Mean time for equilibration and the area under curve values AUC were determined from buffer concentration time profiles, whereas degree of drug uptake and permeation coefficient across erythrocyte membranes were estimated from the erythrocyte concentration time profiles. For all conditions, equilibrium between buffer and erythrocytes was achieved within 15 min, and there was a linear correlation between the AUC values and CPZ dose. When erythrocyte suspension was used, uptake was found to be influenced by both concentration and hematocrit. On the other hand, CPZ uptake about 34% was not influenced by drug concentration when whole blood suspension was used. In addition, in all conditions, the permeation coefficients for CPZ was found to be in the range of 0.34-6.75x10-6 cm/s.

Keywords

Chlorpromazine Hydrochloride, Erythrocytes, Hematocrit, Permeation Coefficient

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