納米氧化鐵(Ferumoxytol)被批準(zhǔn)用于治療患有慢性腎臟疾病(CKD)成年患者的缺鐵性貧血(IDA),。目前已經(jīng)開展了納米氧化鐵對(duì)所有類型的缺鐵性貧血患者的治療效果的研究,。
2015年3月《臨床藥代動(dòng)力學(xué)》(Clinical Pharmacokinetics)雜志發(fā)表了一項(xiàng)關(guān)于納米氧化鐵藥動(dòng)學(xué)研究，該研究對(duì)納米氧化鐵在健康人群和CKD并進(jìn)行血液透析的患者人群中的藥代動(dòng)力學(xué)(PK)進(jìn)行了研究,，并對(duì)納米氧化鐵在所有類型的缺鐵性貧血患者人群中的藥動(dòng)學(xué)行為進(jìn)行了預(yù)測(cè),。
數(shù)據(jù)分析通過NONMEM進(jìn)行,，選擇的參數(shù)包括協(xié)變量測(cè)試。測(cè)定結(jié)果確定了血液透析過程中體積分布是否發(fā)生了變化,，并且提高了模型的擬合度,。最終獲得的模型被用來(lái)模擬健康志愿者、進(jìn)行血液透析的CKD患者以及未進(jìn)行血液透析的CKD患者的藥動(dòng)學(xué)行為,。
結(jié)果顯示Ferumoxytol的消除曲線為非線性二室模型。在血液透析過程中,，中央室V1降低了0.198 L / h,。初始V1在每公斤體重增加了0.614%，女性比男性低了18.3%,。單劑量510 mg時(shí),，健康受試者和CKD非透析患者之間存在差異：Cmax分別為209和204毫ng/mL,，AUCinf為5980和5920 ng/h·mL
結(jié)果表明，健康人與CKD患者的納米氧化鐵藥動(dòng)學(xué)參數(shù)存在差異,，該研究獲得的藥動(dòng)學(xué)參數(shù)能夠?qū)ζ渌愋偷腎DA患者的藥動(dòng)學(xué)進(jìn)行預(yù)期。
參考文獻(xiàn)：Plock, N et al. Clinical Pharmacokinetics. 2015;54(4):385-395
英文鏈接：Population Pharmacokinetic meta-Analysis to Bridge Ferumoxytol Plasma Pharmacokinetics Across Populations.
http://link.springer.com/article/10.1007%2Fs40262-014-0203-9
Population Pharmacokinetic meta-Analysis to Bridge Ferumoxytol Plasma Pharmacokinetics Across Populations
原文摘要：
Background Ferumoxytol is approved for the treatment of iron-deficiency anaemia (IDA) in adult patients with chronic kidney disease (CKD). Ferumoxytol has recently been investigated for use in all-cause IDA. This analysis was employed to bridge ferumoxytol pharmacokinetics (PK) across populations of healthy subjects and patients with CKD on haemodialysis, and to then make informed inferences regarding the PK behaviour of ferumoxytol in the all-cause IDA population.
Methods The data analysis was performed using NONMEM. Selected parameters were included for covariate testing. Investigations to determine if changes in volume of distribution during haemodialysis improved the model fit were also conducted. The final model was used to simulate PK in healthy volunteers (HVs) and CKD patients with and without haemodialysis.
Results The final model was a two-compartment model with non-linear elimination. During haemodialysis, the central volume V1 was estimated to be reduced by 0.198 L/h. A positive relationship was identified between initial V1 and observed weight loss during haemodialysis. V1 increased by 0.614 % per kilogram of body weight, and females had an 18.3 % lower V1 than males. Differences between simulated profiles for different populations were marginal: maximum concentration (C (max)) of 209 vs. 204 ng/mL and area under the curve from time zero to infinity (AUC(inf)) of 5,980 vs. 5,920 ng center dot h/mL in HVs and CKD non-haemodialysis patients, respectively, for a single dose of 510 mg.
Conclusions The results indicate that ferumoxytol PK are comparable between HVs and CKD patients. Furthermore, the results are representative of the PK in other populations and can be used to bridge to subjects with general IDA.
