DESCRIPTION
Darvon® (Propoxyphene Hydrochloride, USP) is an odorless, white crystalline powder with
a bitter taste. It is freely soluble in water. Chemically, it is (2S,3R)-(+)-4-(Dimethylamino)-3-
methyl-1,2-diphenyl-2-butanol propionate (ester) hydrochloride, which can be represented by
the accompanying structural formula. Its molecular weight is 375.94.
Each Pulvule® contains 65 mg (172.9 µmol) (No. 365) propoxyphene hydrochloride. It also contains FD&C Red No. 33, FD&C Yellow No. 6, gelatin, magnesium stearate, silicone, starch, titanium dioxide, and other inactive ingredients.
Each Darvon Compound-65 Pulvule® contains 65 mg (172.9 µmol) propoxyphene hydrochloride, 389 mg (2,159 µmol) aspirin, and 32.4 mg (166.8 µmol) caffeine.
Darvon Compound-65 contains FD&C Red No. 3, FD&C Yellow No. 6, gelatin, glutamic acid hydrochloride, iron oxide, kaolin, silicone, titanium dioxide, and other inactive ingredients.
Propoxyphene Napsylate, USP is an odorless, white crystalline powder with a bitter taste. It is very slightly soluble in water and soluble in methanol, ethanol, chloroform, and acetone. Chemically, it is ((alpha)S,1R)-(alpha)-[2-(Dimethylamino)-1-methylethyl]-(alpha)-phenylphenethyl propionate compound with 2-naphthalenesulfonic acid (1:1) monohydrate, which can be represented by the accompanying structural formula:
Its molecular weight is 565.72
Propoxyphene napsylate differs from propoxyphene hydrochloride in that it allows more stable liquid dosage forms and tablet formulations. Because of differences in molecular weight, a dose of 100 mg (176.8 µmol) of propoxyphene napsylate is required to supply an amount of propoxyphene equivalent to that present in 65 mg (172.9 µmol) of propoxyphene hydrochloride.
The acetaminophen component is 4′-Hydroxyacetanilide, a white, odorless, crystalline powder
possessing a slightly bitter taste, and is represented by the following structural formula:
Each tablet of Darvon-N contains 100 mg (176.8 µmol) propoxyphene napsylate. The tablet also contains cellulose, cornstarch, iron oxides, lactose, magnesium stearate, silicon dioxide, stearic acid, and titanium dioxide.
Each tablet of Darvocet-N 50 contains 50 mg (88.4 µmol) propoxyphene napsylate and 325 mg (2,150 µmol) acetaminophen.
Each tablet of Darvocet-N 100 contains 100 mg (176.8 µmol) propoxyphene napsylate and 650 mg (4,300 µmol) acetaminophen.
Each tablet of Darvocet-N also contains amberlite, cellulose, FD&CYellow No. 6, magnesium stearate, stearic acid, titanium dioxide, and other inactive ingredients.
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CLINICAL PHARMACOLOGY
Propoxyphene is a centrally acting narcotic analgesic agent. Equimolar doses of propoxyphene hydrochloride or napsylate provide similar plasma concentrations. Following administration of 65, 130, or 195 mg of propoxyphene, the bioavailability of propoxyphene is equivalent to that of 100, 200, or 300 mg respectively of propoxyphene napsylate. Peak plasma concentrations of propoxyphene are reached in 2 to 2 1/2 hours. After a 65-mg oral dose of propoxyphene hydrochloride or a 100-mg oral dose of propoxyphene napsylate, peak plasma levels of 0.05 to 0.1 µg/mL are achieved. As shown in Figure 1, the napsylate salt tends to be absorbed more slowly than the hydrochloride. At or near therapeutic doses, this absorption difference is small when compared with that among subjects and among doses.
Figure 1. Mean plasma concentrations of propoxyphene in 8 human subjects following oral administration of 65 and 130 mg of the hydrochloride salt and 100 and 200 mg of the napsylate salt and in 7 given 195 mg of the hydrochloride and 300 mg of the napsylate salt.
Because of this several hundredfold difference in solubility, the absorption rate of very large doses of the napsylate salt is significantly lower than that of equimolar doses of the hydrochloride.
Repeated doses of propoxyphene at 6-hour intervals lead to increasing plasma concentrations, with a plateau after the ninth dose at 48 hours.
Propoxyphene is metabolized in the liver to yield norpropoxyphene. Propoxyphene has a half-life of 6 to 12 hours, whereas that of norpropoxyphene is 30 to 36 hours.
Norpropoxyphene has substantially less central-nervous-system-depressant effect than propoxyphene but a greater local anesthetic effect, which is similar to that of amitriptyline and antiarrhythmic agents, such as lidocaine and quinidine.
In animal studies in which propoxyphene and norpropoxyphene were continuously infused in large amounts, intracardiac conduction time (PR and QRS intervals) was prolonged. Any intracardiac conduction delay attributable to high concentrations of norpropoxyphene may be of relatively long duration.
ACTIONS
Propoxyphene is a mild narcotic analgesic structurally related to methadone. The potency of propoxyphene hydrochloride and propoxyphene napsylate is from two thirds to equal that of codeine.
The combination of propoxyphene with a mixture of aspirin and caffeine produces greater analgesia than that produced by either propoxyphene or aspirin and caffeine administered alone.
Darvocet-N 50 and Darvocet-N 100 provide the analgesic activity of propoxyphene napsylate and the antipyretic-analgesic activity of acetaminophen.
The combination of propoxyphene and acetaminophen produces greater analgesia than that produced by either propoxyphene or acetaminophen administered alone.
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