aprepitant and Kidney-Failure--Chronic

People with gastroparesis who develop treatment-resistant (refractory) disease pose a difficult challenge, especially in the setting of end-stage renal disease (ESRD) or post pancreas transplant. Aprepitant (a neurokinin-receptor antagonist) is licensed for the short-term treatment of chemotherapy-induced nausea. There is lack of information on its long-term efficacy and safety in people with diabetic gastroparesis.. Case 1 was 73-year-old man with Type 2 diabetes of 25 years' duration and ESRD requiring dialysis. He was referred to our unit as his severe symptoms of gastroparesis had failed to respond to multiple medications and resulted in frequent hospital admissions. Aprepitant, which can be used in ESRD, resulted in significant improvement in his symptoms of nausea and vomiting within weeks, and he remained on this long term (18 months) with continued benefits and had no further gastroparesis-related hospital admissions. Case 2 was a 44-year-old man with Type 1 diabetes of 41 years' duration with a history of severe hypoglycaemic events that required a pancreas transplant. Despite normoglycaemia, his symptoms of gastroparesis persisted and failed to respond to multiple medications and frequent botulinum toxin injections. He was commenced on aprepitant with significant improvement in symptoms and has remained on treatment for 12 months with sustained benefits.. We describe two cases in which long-term aprepitant treatment proved effective in alleviating severe symptoms of gastroparesis that had failed to respond to conventional first-line medical treatments. Our cases highlight the need for novel treatments for managing refractory diabetic gastroparesis.

Topics: Adult; Aged; Aprepitant; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Gastric Emptying; Gastroparesis; Humans; Kidney Failure, Chronic; Male; Morpholines; Pancreas Transplantation; Time Factors; Treatment Outcome

The neurokinin NK(1)-receptor antagonist aprepitant has demonstrated efficacy in preventing highly emetogenic chemotherapy-induced nausea and vomiting.. The objective of the present study was to investigate the effects of impaired renal function on the pharmacokinetics and safety of aprepitant.. A total of 32 patients and healthy subjects were evaluated in this open-label, two-part study. Pharmacokinetic parameters after a single oral dose of aprepitant 240 mg were measured in eight patients with end-stage renal disease (ESRD) requiring haemodialysis, eight patients with severe renal insufficiency (SRI [24-hour creatinine clearance <30 mL/min/1.73 m(2)]) and 16 healthy and age-, sex- and weight-matched subjects (controls).. In ESRD patients, the area under the plasma concentration-time curve (AUC) from 0 to 48 hours (AUC(48)) for aprepitant was on average approximately 36% lower than that observed in control subjects (ratio [ESRD patients/healthy controls] of geometric means = 0.64), but the 90% confidence interval 0.52, 0.78 for the ratio of true mean AUC(48) fell within the predefined target interval of 0.5, 2.0. Also in ESRD patients, there was no statistically or clinically significant difference in unbound aprepitant AUC (which may be more clinically relevant than total aprepitant AUC) when compared with healthy control subjects. Aprepitant pharmacokinetic parameters in ESRD patients were clinically similar when haemodialysis was initiated at 4 hours or 48 hours after aprepitant administration. In SRI patients, the ratio (SRI patients/healthy controls) of aprepitant AUC from zero to infinity (AUC(infinity)) geometric mean value was 0.79 with a 90% confidence interval of 0.56, 1.10. On average, in SRI patients the principal aprepitant pharmacokinetic parameters (AUC(infinity), initial maximum plasma concentration [C(max)], time to initial C(max), and apparent elimination half-life) were not statistically different from those obtained in healthy control subjects. Aprepitant was generally well tolerated in both ESRD and SRI patients.. The results of this study demonstrate that ESRD, haemodialysis and SRI have no clinically meaningful effect on aprepitant pharmacokinetics. Therefore, no dosage adjustment of aprepitant is warranted in SRI or ESRD patients.

Topics: Adult; Antiemetics; Aprepitant; Area Under Curve; Blood Proteins; Female; Half-Life; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Morpholines; Neurokinin-1 Receptor Antagonists; Prospective Studies; Protein Binding; Renal Dialysis