School of Engineering, University of Warwick, Coventry, West Midlands, UK.
Clinical Science, Bayer Healthcare, Barmen, Germany.
CPT Pharmacometrics Syst Pharmacol. 2018 Aug;7(8):491-498. doi: 10.1002/psp4.12308. Epub 2018 Jul 2.
This study uses a highly fidelity computational simulator of pulmonary physiology to evaluate the impact of a soluble guanylate cyclase (sGC) modulator on gas exchange in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) as a complication. Three virtual patients with COPD were configured in the simulator based on clinical data. In agreement with previous clinical studies, modeling systemic application of an sGC modulator results in reduced partial pressure of oxygen (PaO ) and increased partial pressure of carbon dioxide (PaCO ) in arterial blood, if a drug-induced reduction of pulmonary vascular resistance (PVR) equal to that observed experimentally is assumed. In contrast, for administration via dry powder inhalation (DPI), our simulations suggest that the treatment results in no deterioration in oxygenation. For patients under exercise, DPI administration lowers PH, whereas oxygenation is improved with respect to baseline values.
本研究使用一种高度逼真的肺生理计算模拟器来评估可溶性鸟苷酸环化酶（sGC）调节剂对慢性阻塞性肺疾病（COPD）和作为并发症的肺动脉高压（PH）患者气体交换的影响。根据临床数据，在模拟器中配置了三个 COPD 虚拟患者。与先前的临床研究一致，如果假设药物引起的肺血管阻力（PVR）降低等于实验中观察到的那样，那么对全身应用 sGC 调节剂进行建模会导致动脉血氧分压（PaO ）降低和二氧化碳分压（PaCO ）升高。相比之下，对于干粉吸入（DPI）给药，我们的模拟表明，治疗不会导致氧合恶化。对于运动中的患者，DPI 给药可降低 PH，而与基线值相比，氧合得到改善。
