Table 4.

Peripherally Acting μ-Opioid Receptor Antagonist (PAMORAs) in Patients with CKD

	Route of Administration	Absorption Tmax (Hours)	Distribution	Metabolism	Elimination T1/2 (Hours)	Standard Dose in General Population	Use in CKD Patients	Use in HD Patients
Methylnaltrexone	Oral; Subcutaneous	Oral: 1.5 hrs (delayed by 2 hrs with high-fat meals). Subcutaneous: 30 min.	Vss: 1.1L/Kg	- Sulfation (Phase II) to methylnaltrexone-3-sulfate - Carbonyl reduction (Phase I) to methyl-6-naltrexol and methyl-6β-naltrexol	8	8 mg (0.4 mL for body weight 38–61 kg) 12 mg (0.6 mL for body weight 62–114 kg)	Dose reduction required in patients with moderate to severe CKD: - 4 mg for body weight ≤ 61 kg - 8 mg for body weight 62–114 kg	Not recommended (no data)
Naloxegol	Oral	< 2hrs in most of subjects a secondary Cmax occurs approx 0.4–3 hrs after the first Cmax	Vz/F: 968–2.140 L	CYP3A (Phase I) N-dealkylation O-demethylation Oxidation Partial loss of the PEG chain	6–11	25 mg daily	Dose reduction required in patients with moderate to severe CKD: 12.5 mg as starting dose	NA
Naldemedine	Oral	0.75 hr; 2.5 hr (with food)	Vz/F: 155 L	- CYP3A4 (Phase I) to nor-naldemedine - Glucuronidation (Phase II) to naldemedine-3-glucuronide	11	200 mcg daily	No dose adjustment is required at any stage of CKD, including ESRD	No dose adjustment is required for HD patients. Not removed by HD.

Abbreviations: C_max, peak plasma drug concentration; V_z/F, apparent volume of distribution during terminal phase after non-intravenous administration; Vss, apparent volume of distribution at steady-state; t_1/2, elimination half-life; T_max, time to reach maximum (peak) plasma concentration following drug administration at steady state.

Note: Data from Raffa RB, Taylor R Jr, Pergolizzi JV Jr. Treating opioid-induced constipation in patients taking other medications: avoiding CYP450 drug interactions. J Clin Pharm Ther. 2019;44(3):361–371. doi:10.1111/jcpt.12812.103