Molecular mass: 318.414 g/mol PubChem compound: 86278362
Pegvaliase-pqpz is a PEGylated phenylalanine ammonia lyase (PAL) enzyme that converts phenylalanine to ammonia and trans‑cinnamic acid. It substitutes for the deficient phenylalanine hydroxylase (PAH) enzyme activity in patients with PKU and reduces blood phenylalanine concentrations.
Pegvaliase treatment of adult patients with PKU resulted in the reduction of blood phenylalanine concentrations from pre-treatment baseline. The reduction of blood phenylalanine concentrations diminished with decreased pegvaliase‑pqpz plasma concentrations.
The pharmacokinetics of pegvaliase‑pqpz exhibit high inter-patient and intra-patient variability due to the heterogeneity of the immune response in adult patients with PKU. Higher antibody titers correlated with higher apparent clearance of pegvaliase‑pqpz. In the first eight weeks of induction/titration treatment, plasma pegvaliase‑pqpz concentrations were low to not measurable. At steady state during maintenance treatment with pegvaliase 20 mg, 40 mg, and 60 mg subcutaneously once daily, the mean ± SD (range) plasma trough pegvaliase‑pqpz concentrations were: 11.2 ± 9.0 (0.21 to 29.6) mg/L, 10.4 ± 12.7 (0.18 to 43.1) mg/L and 4.8 ± 10.7 (0 to 39.7) mg/L, respectively. The following pharmacokinetic parameters were observed in adult patients with PKU treated with pegvaliase at maintenance dosages of 20 mg once daily and 40 mg once daily.
The median Tmax was approximately 8 hours. The mean ± SD (range) peak concentration (Cmax) at steady state was: 14.0 ± 16.3 (0.26 to 68.5) mg/L and 16.7 ± 19.5 (0.24 to 63.8) mg/L, respectively.
The mean ± SD (range) apparent volume of distribution was 26.4 ± 64.8 (1.8 to 241) L and 22.2 ± 19.7 (3.1 to 49.5) L, respectively.
The mean ± SD (range) apparent clearance at steady state was 0.39 ± 0.87 (0.018 to 3.66) L/h and 1.25 ± 2.46 (0.034 to 8.88) L/h, respectively. The mean ± SD (range) half-life was 47 ± 42 (14 to 132) hours and 60 ± 45 (14 to 127) hours, respectively.
The metabolism of phenylalanine ammonia lyase is expected to occur via catabolic pathways and be degraded into small peptides and amino acids.
The route of elimination of pegvaliase‑pqpz has not been studied in humans.
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