Mascarenhas Maria R, Mondick John, Barrett Jeffrey S, Wilson Martha, Stallings Virginia A, Schall Joan I
Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Metrum Institute, Tariffville, CT, USA.
J Clin Pharmacol. 2015 Aug;55(8):854-65. doi: 10.1002/jcph.484. Epub 2015 Mar 23.
The malabsorption blood test (MBT), consisting of pentadecanoic acid (PA), a free fatty acid, and triheptadecanoic acid (THA), a triglyceride that requires pancreatic lipase for absorption of the heptadecanoic acid (HA), was developed to assess fat malabsorption in patients with cystic fibrosis (CF) and pancreatic insufficiency (PI). The objective was to construct a population pharmacokinetic (PK) model to describe PA and HA disposition in healthy subjects and CF subjects. A model was simultaneously fit to PA and HA concentrations, consisting of 1-compartment disposition and a transit model to describe absorption. PA bioavailability estimates for CF subjects without pancreatic enzyme administration (1.07 [0.827, 1.42]) and with enzymes (0.88 [0.72, 1.09]) indicated PA absorption comparable to healthy subjects. HA bioavailability in CF without enzyme administration was 0.0292 (0.0192, 0.0459) and with enzymes increased to 0.606 (0.482, 0.823). In CF, compared with taking enzymes with the MBT, HA bioavailability was further decreased by factors of 0.829 (0.664, 0.979) and 0.78 (0.491, 1.13) with enzymes taken 30 and 60 minutes after MBT, respectively. The MBT detected differences in fat absorption in subjects with CF with and without enzyme administration and with changes in enzyme timing. Future studies will address application of the MBT in CF and other malabsorption diagnoses.
由游离脂肪酸十五烷酸(PA)和甘油三酯十七烷三酸(THA)组成的脂肪吸收不良血液检测(MBT)被开发用于评估囊性纤维化(CF)和胰腺功能不全(PI)患者的脂肪吸收不良情况,其中THA需要胰腺脂肪酶来吸收十七烷酸(HA)。目的是构建一个群体药代动力学(PK)模型来描述健康受试者和CF受试者体内PA和HA的处置情况。一个同时拟合PA和HA浓度的模型,由一室处置模型和描述吸收的转运模型组成。未服用胰酶的CF受试者(1.07 [0.827, 1.42])和服用胰酶的CF受试者(0.88 [0.72, 1.09])的PA生物利用度估计值表明,PA吸收情况与健康受试者相当。未服用酶的CF患者中HA的生物利用度为0.0292(0.0192, 0.0459),服用酶后增加到了0.606(0.482, 0.823)。在CF患者中,与在进行MBT检测时服用酶相比,在MBT检测后30分钟和60分钟服用酶时,HA的生物利用度分别进一步降低了0.829(0.664, 0.979)和0.78(0.491, 1.13)。MBT检测出了服用和未服用酶以及酶服用时间变化的CF受试者脂肪吸收的差异。未来的研究将探讨MBT在CF和其他吸收不良诊断中的应用。