Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

12.2 Pharmacodynamics
Approximately 24 hours following the first dose of KRYSTEXXA®, mean plasma uric acid levels for subjects in the KRYSTEXXA® groups were 0.7 mg/dL for the KRYSTEXXA® 8 mg every 2 weeks group.
In comparison, the mean plasma uric acid level for the placebo group was 8.2 mg/dL.

In a single-dose, dose-ranging trial, following 1-hour intravenous infusions of 0.5, 1, 2, 4, 8 or 12 mg of pegloticase in 24 patients with symptomatic gout (n=4 subjects/dose group), plasma uric acid decreased with increasing pegloticase dose or concentrations. The duration of suppression of plasma uric acid appeared to be positively associated with pegloticase dose. Sustained decrease in plasma uric acid below the solubility concentration of 6 mg/dL for more than 300 hours was observed with doses of 8 mg and 12 mg.

Pharmacokinetic Properties

12.3 Pharmacokinetics
Pegloticase levels were determined in serum based on measurements of uricase enzyme activity.

Absorption
Following single intravenous infusions of 0.5 mg to 12 mg pegloticase in 23 patients with symptomatic gout, maximum serum concentrations of pegloticase increased in proportion to the dose administered.
The population pharmacokinetic analysis showed that age, sex, weight, and creatinine clearance did not influence the pharmacokinetics of pegloticase.

Distribution
Significant covariates included in the model for determining clearance and volume of distribution were found to be body surface area and anti-pegloticase antibodies.

Special Populations
Pediatric Populations
The pharmacokinetics of pegloticase has not been studied in children and adolescents.

Patients with Renal or Hepatic Impairment
No formal studies were conducted to examine the effects of either renal or hepatic impairment on pegloticase pharmacokinetics.