Shionoiri H, Naruse M, Minamisawa K, Ueda S, Himeno H, Hiroto S, Takasaki I
Second Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Clin Pharmacokinet. 1997 Jun;32(6):460-80. doi: 10.2165/00003088-199732060-00003.
Fosinopril is a phosphorus-containing ester prodrug of an angiotensin-converting enzyme (ACE) inhibitor. It is hydrolysed mainly in the gastrointestinal mucosa and liver to the active diacid, fosinoprilat, which has unique pharmacological properties. The majority of the active moieties of other ACE inhibitors are excreted in the urine. This means that an adjustment in either the dosage and/or the administration interval is needed in patients with moderate to severe renal dysfunction, in order to reduce drug accumulation and the possibility of an excessive decrease in blood pressure or other adverse effects. On the other hand, fosinoprilat is excreted both in urine and bile (as with temocaprilat, zofenoprilat and spiraprilat), and thus an adjustment of dosage and/or administration interval may be unnecessary in patients with moderate to severe renal dysfunction, as impaired renal function influences little of the pharmacokinetics of fosinoprilat. Furthermore, the available evidence suggests that the pharmacokinetic variables of fosinoprilat in patients receiving haemodialysis were similar to those in patients with moderate to severe renal dysfunction. Dosage modifications or supplemental dose administration following dialysis may be unnecessary. The hypotensive effect of the combination of fosinopril and a diuretic is synergistic. Pharmacokinetic interactions with fosinopril are unlikely in patients receiving thiazide or loop diuretics. Fosinopril has beneficial effects for patients with hypertension and left ventricular hypertrophy because it produces an adequate reduction in blood pressure and reversal of left ventricular hypertrophy. There are a large number of studies of the pharmacokinetics of fosinopril. However studies of its pharmacokinetic drug interactions with other drugs are far fewer. Further investigations are needed in several clinical settings.
福辛普利是一种含磷酯的前药，属于血管紧张素转换酶（ACE）抑制剂。它主要在胃肠道黏膜和肝脏中水解为活性二酸福辛普利拉，福辛普利拉具有独特的药理特性。其他ACE抑制剂的大部分活性部分经尿液排泄。这意味着中重度肾功能不全患者需要调整剂量和/或给药间隔，以减少药物蓄积以及血压过度下降或出现其他不良反应的可能性。另一方面，福辛普利拉经尿液和胆汁排泄（替莫普利拉、佐芬普利拉和螺普利拉也是如此），因此中重度肾功能不全患者可能无需调整剂量和/或给药间隔，因为肾功能受损对福辛普利拉的药代动力学影响较小。此外，现有证据表明，接受血液透析患者的福辛普利拉药代动力学变量与中重度肾功能不全患者相似。透析后可能无需调整剂量或补充给药。福辛普利与利尿剂联合使用时的降压作用具有协同性。接受噻嗪类或襻利尿剂治疗的患者与福辛普利发生药代动力学相互作用的可能性不大。福辛普利对高血压和左心室肥厚患者有益，因为它能充分降低血压并逆转左心室肥厚。关于福辛普利药代动力学的研究有很多。然而，其与其他药物的药代动力学药物相互作用的研究要少得多。在几种临床情况下还需要进一步研究。
