Drug information of Glycerol Phenylbutyrate

Glycerol Phenylbutyrate

Drug group:

It is used to treat urea cycle problems.

Mechanism of effect

Decreases elevated plasma ammonia glutamine levels

Pre-prodrug that is metabolized by ester hydrolysis and pancreatic lipases to phenylbutyrate (PBA) and then by beta oxidation to phenylacetate (PAA); glutamine is conjugated with phenylacetate to form phenylacetylglutamine (PAGN), a nitrogen waste product that is excreted renally

The phenylacetylglutamine conjugate provides an alternate vehicle to urea for waste nitrogen excretion; for each gram of sodium phenylbutyrate administered, it is estimated that between 0.12–0.15 grams of phenylacetylglutamine nitrogen are produced


Peak plasma time: 2 hr (PBA), 4 hr (PAA), 4 hr (PAGN)

Peak plasma concentration: 37 mcg/mL (PBA), 14.9 mcg/mL (PAA), 30.2 mcg/mL (PAGN)

Protein Bound: 80.6-98% (PBA), 37.1-65.6% (PAA), 7-12% (PAGN)

Glycerol phenylbutyrate metabolized by hydrolyzed by pancreatic lipases and release phenylbutyric acid (PBA); PBA undergoes beta-oxidation to phenylacetic acid (PAA)

PAA is conjugated with glutamine in the liver and kidney through the enzyme phenylacetyl-CoA: L-glutamine-N-acetyltransferase to form PAGN

Excretion: 66.4-68.9% in urine as PAGN

Drug indications

Urea Cycle Disorders


Administer PO in 3 equally divided dosages, each rounded up to nearest 0.5 mL

Not to exceed 17.5 mL/day

Switching from sodium phenylbutyrate to glycerol phenylbutyrate

Total daily dose (mL) = total daily dosage of sodium phenylbutyrate (g) x 0.86

Total daily dose (mL) = total daily dosage of sodium phenylbutyrate powder (g) x 0.81


4.5-11.2 mL/m²/day (5-12.4 g/m²/day)


<2 years: Give PO in 3 or more equally divided dosages, each rounded up to nearest 0.1 mL

≥2 years: Give PO in 3 equally divided dosages, each rounded up to nearest 0.5 mL

Drug contraindications

Hypersensitivity to this drug

Hypersensitivity to phenylbutyrate (eg, wheezing, dyspnea, coughing, hypotension, flushing, nausea, rash)

Side effects

Diarrhea , Headache , nausea , dyspepsia , flatulence , nasal stuffiness , burning sensation in the mouth , tiredness , Abdominal pain , Rash




Children(Neutropenia-Vomiting-Constipation-Diarrhea-Pyrexia-Hypophagia-Cough, nasal congestion-Rhinorrhea-Rash-Papule-Gastroesophageal reflux-Increased hepatic enzymes-Feeding disorder (decreased appetite, hypophagia)-Anemia-Cough-Dehydration-Metabolic acidosis-Thrombocytosis-Thrombocytopenia-Lymphocytosis-Flatulence-Lethargy-Irritability/agitation)

Abdominal pain


Decreased appetite


Ammonia increased



Abnormal body odor, including from skin, hair, and urine

Retching and gagging

Dysgeusia or burning sensation in mouth





Nasal congestion


Rash and papule

triamcinolone acetonide injectable suspension


Safety and efficacy not established for N-acetylglutamate synthase (NAGS) deficiency

Increased exposure to phenylacetate (PAA), the major metabolite, associated with neurotoxicity

Low or absent pancreatic enzymes or intestinal disease resulting in fat malabsorption may result in reduced or absent digestion/absorption of glycerol phenylbutyrate

Points of recommendation

Determine starting dose by patient’s residual urea synthetic capacity, dietary protein requirements, and diet adherence

~47% of dietary nitrogen is excreted as waste and ~70% of phenylbutyrate dose is converted to urinary phenylacetylglutamine (U-PAGN), so an initial estimated dose is 0.6 mL/g dietary protein ingested per day

Monitor plasma ammonia levels

Must be used with dietary protein restriction and, in some cases, dietary supplements (eg, essential amino acids, arginine, citrulline, protein-free calorie supplements)

Pregnancy level



Based on animal data, this drug may cause fetal harm. There are no controlled data in human pregnancy

Breast feeding warning

Unknown if distributed in human breast milk; because of the potential for serious adverse reactions, including neurotoxicity and tumorigenicity in a breastfed infant, advise patients that breastfeeding is not recommended

Related drugs

Sodium phenylbutyrate

Drug forms


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