CLINICAL PHARMACOLOGY
Pentazocine hydrochloride and acetaminophen tablets are an analgesic possessing antipyretic actions.
Pentazocine is an analgesic with agonist/antagonist action which when administered orally is approximately equivalent on a mg for mg basis in analgesic effect to codeine.
Acetaminophen is an analgesic and antipyretic.
Onset of significant analgesia with pentazocine usually occurs between 15 and 30 minutes after oral administration, and duration of action is usually three hours or longer. Onset and duration of action and the degree of pain relief are related both to dose and the severity of pretreatment pain. Pentazocine weakly antagonizes the analgesic effects of morphine, meperidine, and phenazocine; in addition, it produces incomplete reversal of cardiovascular, respiratory, and behavioral depression induced by morphine and meperidine. Pentazocine has about 1/50 the antagonistic activity of nalorphine. It also has a sedative activity.
Pentazocine is well absorbed from the gastrointestinal tract. Plasma levels closely correspond to the onset, duration, and intensity of analgesia. The time to mean peak concentration in 24 normal volunteers was 1.7 hours (range 0.5 to 4 hours) after oral administration and the mean plasma elimination half-life was 3.6 hours (range 1.5 to 10 hours).
The action of pentazocine is terminated for the most part by biotransformation in the liver with some free pentazocine excreted in the urine. The products of the oxidation of the terminal methyl groups and glucuronide conjugates are excreted by the kidney. Elimination of approximately 60% of the total dose occurs within 24 hours. Pentazocine passes the placental barrier.
Onset of significant analgesic and antipyretic activity of acetaminophen when administered orally occurs within 30 minutes and is maximal at approximately 21/2 hours. The pharmacological mode of action of acetaminophen is unknown at this time.
Acetaminophen is rapidly and almost completely absorbed from the gastrointestinal tract. In 24 normal volunteers the mean time to peak plasma concentration was 1 hour (range 0.25 to 3 hours) after oral administration and the mean plasma elimination half-life was 2.8 hours (range 2 to 4 hours).
The effect of pentazocine on acetaminophen plasma protein binding or vice versa has not been established. For acetaminophen there is little or no plasma protein binding at normal therapeutic doses. When toxic doses of acetaminophen are ingested and drug plasma levels exceed 90 mcg/mL, plasma binding may vary from 8% to 43%.
Acetaminophen is conjugated in the liver with glucuronic acid and to a lesser extent with sulfuric acid. Approximately 80% of acetaminophen is excreted in the urine after conjugation and about 3% is excreted unchanged. The drug is also conjugated to a lesser extent with cysteine and additionally metabolized by hydroxylation.
If pentazocine hydrochloride and acetaminophen tablets are taken every 4 hours over an extended period of time, accumulation of pentazocine and to a lesser extent, acetaminophen, may occur.
|
