Table 1 Key drug features of sodium benzoate (NaBZ), sodium phenylbutyrate (NaPBA) and glycerol phenylbutyrate (GPB)
|  | Sodium benzoatea NaBZb | Sodium phenylbutyrate [20] NaPBAb | Glycerol phenylbutyrate (Ravicti®) [21] GPBb |
|---|---|---|---|
European Medicines Agency (EMA) approval date | NAa | 1999 [20] | 2015 [21] |
Dosage | 250 mg/kg/day maximum: 12 g/day [3] | 450–600 mg/kg/day in children weighing less than 20 kg 9.9–13.0 g/m2/day in children weighing more than 20 kg, adolescents and adults [20] The safety and efficacy of doses in excess of 20 g/day (40 tablets) has not been established [20] | The recommended total daily dose is based on body surface areac—ranges from: 4.5 ml/m2/day to 11.2 ml/m2/day [5.3 g/m2/day to 12.4 g/m2/day) [21] |
Formulation/Preparation | Powder (dissolved in liquid and oral administration). Dispensed differently by for example hospital pharmaciesa | Tablets or granules (measure with a dosing spoon and mix with solid foods or liquid foods) for oral administration [20] | Oral liquid (measure with a syringe) [21] |
Frequency of administration | 3–4 times per day [3] | With each meal or feeding (e.g., 4–6 times per day in small children) [20] | With each meal or feeding (e.g., 3 to 6 times per day) [21] |
Taste | May taste salty, sweet, bitter, sour and sticky [22] | Bad taste [23] | Minimal taste [24] |
Efficacy | Not evaluated in randomized clinical trialsa | No randomized control trial was included for the EMA approval for NaPBA but the pivotal study for GPB met its predefined endpoint of non-inferiority to NaPBA with respect to ammonia control [21, 23] | Phase 2 comparison showed noninferiority of GPB to NaPBA with respect to ammonia control [21, 24] Post hoc analysis demonstrated ammonia was lower after treatment with GPB compared to NaPBA [21, 24] |