GENERIC NAME : Pharmacokinetics HUMAN : Methocarbamol : Methocarbamol is effective in reducing muscle spasm and pain in acute musculoskeletal disorders secondary to trauma and inflammation. Each drug combination of methocarbamol and acetylsalicylic acid contributed to the therapeutic effects against acute painful musculoskeletal problems of spasms , pain and tenderness . Methocarbamol administered orally is well absorbed from the gastrointestinal tract . Animal studies indicate that absorption occurs in the small intestine. Studies in humans receiving doses of methocarbamol radio labeling (C14 ) indicated that 97-99 % of the administered radioactivity was recovered in the urine after 3 days . In a comparative bioavailability study , peak plasma concentrations after oral administration was reached in about 45 minutes when methocarbamol was administered in combination with ibuprofen . The plasma half- life of methocarbamol was administered only 0.27 hours and 1.25 + 1.30 + 0.29 hours when administered in combination. In a single proportionality study doses of 500 mg , 1500 mg and 3000 mg , showed that the kinetics of methocarbamol is nonlinear. However, clearance rates suggest that no accumulation is expected with chronic dosing every 6 hours. In humans, has shown methocarbamol metabolized by dealkylation, hydroxylation and conjugation with glucuronic acid and sulfate , presumably in the liver . The two metabolites identified are: 3 ( 2 -hydroxyphenoxy ) 1 1,2 propanediol carbamate and 3 (4-hydroxy -2-methoxyphenoxy ) -1,2- propanediol 1 carbamate . Extremely small amounts of unchanged methocarbamol have been recovered in the feces. The precise mechanism of action is unknown . It is thought that methocarbamol acts on the central nervous system, perhaps depressing polysynaptic reflexes . Ibuprofen : Ibuprofen , like all anti -inflammatory drugs drugs ( NSAIDs) is an analgesic , antipyretic and anti – inflammatory medication. There is strong evidence to support the view that the major mechanism of action of ibuprofen ( as other NSAIDs) is decreased relative to the biosynthesis of prostaglandins . Ibuprofen is rapidly and almost completely absorbed . The peak serum concentration occurs within 1-2 hours in adults . In a comparative bioavailability study after oral administration the plasma concentration peak at approximately 1.6 hours for ibuprofen alone and in about 1.3 hours was reached when ibuprofen is administered in combination with methocarbamol . The plasma half- life of ibuprofen administered alone was 2.11 ± 0.43 hours , and 2.08 ± 0.37 hours when administered in combination. Food decreases the rate but not the extent of absorption . The volume of distribution in adults after oral administration is 0.1 – 0.2 lt./kg.3 At therapeutic concentrations , ibuprofen is highly bound to human plasma and whole site II purified albumin . With repeated dosing, no accumulation of ibuprofen or its metabolites in plasma appreciable . In humans, levels of the drug found in the synovial fluid of inflamed tissue about 5 to 12 hours after oral administration. We have identified the cytochrome P450 ( CYP) 2C9 as the most important for the formation of all oxidative metabolites of R- catalyst ( -) and S -(+ ) ibuprofen. Approximately 80 % of a dose recovered in the urine , mainly as conjugates carboximetabolitos and hydroxy metabolites . Ibuprofen does not appear to induce the formation of drug metabolizing enzymes in rats . No evidence for differential metabolism or elimination of ibuprofen in adulthood. Pharmacokinetic evaluation of ibuprofen in elderly subjects ( 65-78 years) compared with young adult subjects ( 22-35 years) found no clinically significant difference in the kinetic profiles of ibuprofen for these age groups . Additionally , no statistically significant difference between the two populations in the pattern of urinary excretion of the drug and its major metabolites .
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