Phrenilin (Butalbital / Acetaminophen) - Description and Clinical Pharmacology

Rx Only

DESCRIPTION

PHRENILIN^®: Each PHRENILIN^® tablet for oral administration, contains Butalbital, USP 50 mg, Acetaminophen, USP 325 mg.

In addition each PHRENILIN^® tablet contains the following inactive ingredients: alginic acid, corn starch, D&C Red No. 27 - Aluminum Lake, FD&C Blue No. 1 - Aluminum Lake, gelatin, magnesium stearate, microcrystalline cellulose and pregelatinized starch.

PHRENILIN^® FORTE: Each PHRENILIN^® FORTE capsule for oral administration, contains Butalbital, USP 50 mg, Acetaminophen, USP 650 mg.

In addition each PHRENILIN^® FORTE capsule may also contain the following inactive ingredients: benzyl alcohol, butylparaben, D&C Red No. 28, D&C Red No. 33, edetate calcium disodium, FD&C Blue No. 1, FD&C Red No. 40, gelatin, methylparaben, propylparaben, silicon dioxide, sodium lauryl sulfate, sodium propionate and titanium dioxide.

Butalbital (5-allyl-5-isobutylbarbituric acid), a slightly bitter, white, odorless, crystalline powder, is a short to intermediate-acting barbiturate. It has the following structural formula:

C₁₁H₁₆N₂O₃                     M.W. = 224.26

Acetaminophen (4'-hydroxyacetanilide), a slightly bitter, white, odorless, crystalline powder, is a non-opiate, non-salicylate analgesic and antipyretic. It has the following structural formula:

C₈H₉NO₂          M.W. = 151.16

CLINICAL PHARMACOLOGY

This combination drug product is intended as a treatment for tension headache.

It consists of a fixed combination of butalbital and acetaminophen. The role each component plays in the relief of the complex of symptoms known as tension headache is incompletely understood.

Pharmacokinetics: The behavior of the individual components is described below.

Butalbital: Butalbital is well absorbed from the gastrointestinal tract and is expected to distribute to most tissues in the body. Barbiturates in general may appear in breast milk and readily cross the placental barrier. They are bound to plasma and tissue proteins to a varying degree and binding increases directly as a function of lipid solubility.

Elimination of butalbital is primarily via the kidney (59% to 88% of the dose) as unchanged drug or metabolites. The plasma half-life is about 35 hours. Urinary excretion products include parent drug (about 3.6% of the dose), 5-isobutyl-5-(2,3-dihydroxy-propyl) barbituric acid (about 24% of the dose), 5-allyl-5 (3-hydroxy-2-methyl-1-propyl) barbituric acid (about 4.8% of the dose), products with the barbituric acid ring hydrolyzed with excretion of urea (about 14% of the dose), as well as unidentified materials. Of the material excreted in the urine, 32% is conjugated.

See OVERDOSAGE for toxicity information.

Acetaminophen: Acetaminophen is rapidly absorbed from the gastrointestinal tract and is distributed throughout most body tissues. The plasma half-life is 1.25 to 3 hours, but may be increased by liver damage and following overdosage. Elimination of acetaminophen is principally by liver metabolism (conjugation) and subsequent renal excretion of metabolites. Approximately 85% of an oral dose appears in the urine within 24 hours of administration, most as the glucuronide conjugate, with small amounts of other conjugates and unchanged drug.

See OVERDOSAGE for toxicity information.