Methylnaltrexone for Opioid-Induced Constipation in Children
Methylnaltrexone for Opioid-Induced Constipation in Children
The pharmacokinetic profile of methylnaltrexone has been studied in adults, but not children. After subcutaneous administration, methylnaltrexone reaches peak concentrations of 117–140 ng/mL in 0.25–0.5 hrs. It is widely distributed to the tissues, with an estimated volume of distribution of 1 L/kg. Area under the concentration-time curve (AUC) ranges from 175 to 223 ng·hr/mL over the recommended dosing range in adults. Approximately 50% of a dose is cleared by the kidneys as unchanged drug. The remainder undergoes metabolism, primarily through N-methylation and conjugation via sulfotransferases SULT1E1 and SULT2A1. The elimination half-life of methylnaltrexone in healthy adults enrolled in clinical trials has ranged from 7.8 to 13.4 hrs. Clearance is significantly prolonged in patients with renal dysfunction. In a study of 32 adults, mean half-life increased 13.4 ± 4.8 hrs in the healthy controls to 17.5 ± 2 hrs in the patients with mild renal impairment, 18.7 ± 3.9 hrs in those with moderate renal impairment, and 19.6 ± 2.8 hrs in those with severe renal impairment. Hepatic impairment has little effect on half-life or total drug exposure.
Pharmacokinetics
The pharmacokinetic profile of methylnaltrexone has been studied in adults, but not children. After subcutaneous administration, methylnaltrexone reaches peak concentrations of 117–140 ng/mL in 0.25–0.5 hrs. It is widely distributed to the tissues, with an estimated volume of distribution of 1 L/kg. Area under the concentration-time curve (AUC) ranges from 175 to 223 ng·hr/mL over the recommended dosing range in adults. Approximately 50% of a dose is cleared by the kidneys as unchanged drug. The remainder undergoes metabolism, primarily through N-methylation and conjugation via sulfotransferases SULT1E1 and SULT2A1. The elimination half-life of methylnaltrexone in healthy adults enrolled in clinical trials has ranged from 7.8 to 13.4 hrs. Clearance is significantly prolonged in patients with renal dysfunction. In a study of 32 adults, mean half-life increased 13.4 ± 4.8 hrs in the healthy controls to 17.5 ± 2 hrs in the patients with mild renal impairment, 18.7 ± 3.9 hrs in those with moderate renal impairment, and 19.6 ± 2.8 hrs in those with severe renal impairment. Hepatic impairment has little effect on half-life or total drug exposure.
Source...