Naproxen half-life

One study found no adverse interaction between naproxen and cimetidine and no alteration in the beneficial effects of cimeti ne on gastric acid secretion, but another study found that cimetidine caused a moderate 39 to 60% decrease in the naproxen half-life, and a 20 /o reduction in the AUC of naproxen. In one of these studies the half-life of naproxen was reduced by about 40% by ranitidine and 50% by famotidine. A further study found that nizatidine does not affect the pharmacokinetics of naproxen. ... 

Other arylpropionic acids include naproxen, ketopro-fen and flurbiprofen. They share most of the properties of ibuprofen. The daily oral dose of ketoprofen is 50-150 mg, 150-200 mg for flurbiprofen and 250-1000 mg for naproxen. Whereas the plasma elimination half-life of ketoprofen and flurbiprofen are similar to that of ibuprofen (1.5-2.5 h and 2.4-4 h, respectively), naproxen is eliminated much more slowly with a half-life of 13-15 h. 

In Sect. 8.2.3, we have discussed 1-alkyl-l-azacycloalkan-2-ones (8.32, n = 1 or 2 m = 3, 4, 5 or 6) as a group of amidoalkyl esters, taking prodrugs of indomethacin (8.9, R = OH) and naproxen (8.26) as examples [43a,b]. For both compounds, the prodrugs in the series n = 1 were rapidly hydrolyzed (tm ca. 0.5-1 h in pH 7.4 buffer at 32°). Furthermore, the carbinolamides liberated were not fully stable and broke down by hydrolysis to produce the toxic formaldehyde (Fig. 8.3) [62], Thus, the half-life of decomposition of A-(hydroxymethyl)benzamide (HOCH2-NH-CO-C6H5), a pro-moiety of 8.56 discussed below, was 160 h at pH 7.4 and 37° [69]. This means that a small amount of formaldehyde may be formed in vivo. 

Nabumetone is the only nonacid NSAID in current use it is converted to the active acetic acid derivative in the body. It is given as a ketone prodrug that resembles naproxen in structure (Figure 36-1). Its half-life of more than 24 hours (Table 36-1) permits once-daily dosing, and the drug does not appear to undergo enterohepatic circulation. Renal impairment results in a doubling of its half-life and a 30% increase in the area under the curve. 

Naproxen is a naphthylpropionic acid derivative. It is the only NSAID presently marketed as a single enantiomer. Naproxen s free fraction is significantly higher in women than in men, but half-life is similar in both sexes (Table 36-1). Naproxen is effective for the usual rheumatologic indications and is available in a slow-release formulation, as an oral suspension, and over the counter. A topical preparation and an ophthalmic solution are also available. 

The plasma elimination half life of naproxen is about 13 h. Naproxen is heavily bound to plasma proteins (>99%) at therapeutic concentrations. Approximately 95% of the compound is excreted as naproxen and its 6-O-desmethyl metabolite (Davies and Andersson, 1997). 

A lipase-immobilized membrane reactor was applied for the optical resolution of racemic naproxen, lipase stability was enhanced by the EMR set-up to > 200 h in comparison with a half-life of 2 h in a stirred tank. Only pure lipase gave the best enantioselectivity (Sakaki, 2001). 

In another trial the pharmacokinetics of a single dose of naproxen was studied in 11 patients with liver disease (four severe hepatitis with cholestasis two extrahepatic cholestasis one chronic alcoholic cirrhosis two active chronic hepatitis, with and without symptoms one asymptomatic PBC and one asymptomatic hepatic cirrhosis). In two of the seven patients with cholestasis, a significant delay in absorption occurred. In most of the patients studied there was a significant decrease in elimination, increasing the half-life from around 14 hours to 20 hours [41]. 

Average oral bioavailability wide individual dog variation. Naproxen has an unusually long half-life in dogs. 

It has been suggested that the increase in thrombotic cardiovascular events in rofecoxib-treated patients probably represents the antiplatelet effect of naproxen (34,45,46). Naproxen has a long pharmacodynamic half-life and inhibits platelet aggregation by 88% for up to 8 hours (47). 

Naproxen inhibits the metabolism and renal excretion of probenecid, prolonging its half-life (34). 

Various arylpropionic acids show similar specificity. For most, if not all, the (5) enantiomer is the pharmacologically active one, whereas the R) enantiomer is usually much less active, although the ratio of iS)/ R) activity varies from drug to drug (and species to species). Only one of these drugs, however, is administered as the separated (S) enantiomer (naproxen, Naprosyn ). Normally these drugs are considered safe, and one cannot readily differentiate between the relative activities of the (S) and (R) forms because the in vivo half-life is very short, typically one or two hours. In patients with impaired renal function, where clearance is much slower, however, problems can arise. From in vivo studies of ibuprofen, it was established that the (S)-(-l-) isomer was responsible for antiinflammatory activity. In vivo, however, the (/ )-(-) isomer may become active because there is stereoselective inversion from R) to (S) (but not from 5 to R) in vivo with a half-life of about two hours. This inversion apparently proceeds by stereoselective formation of the coenzyme A (CoA) ester of the (f )-(-)-arylpropionic acid, followed by epimerization and release of the (S)-(+)-enantiomer. This epimerization is observed in vivo before the oxidative metabolism. Such inversion from (R) to (S) in vivo is also known for fenoprofen and benoxa-profen, and is expected to occur for most of the drugs of this series. ... 

Naproxen is a propionic acid derivative that has a structure similar to ibuprofen and ketoprofen. It can be administered either i.v. or p.o. to horses, even though it is poorly absorbed with a bioavailability of approximately 50% (Pasargiklian Bianco 1986). It has a relatively short half-life in plasma (4h) (Tobin 1979). There is little information available on the therapeutic index of naproxen in the horse. 

Drug Interactions. Enzyme inducers, such as carbamazepine and phenytoin, increase tiagabine clearance and decrease the half-life. Food decreases the rate but not the extent of absorption. Tiagabine is displaced from protein by naproxen, salicylates, and valproate. However, tiagabine does not displace phenytoin, valproic acid, amitrypty-line, tolbutamide, or warfarin. ... 

Naproxen is absorbed fully when administered orally. Food delays the rate but not the extent of absorption. Peak concentrations in plasma occur within 2 to 4 hours and are somewhat more rapid after the administration of naproxen sodium. Absorption is accelerated by the concurrent administration of sodium bicarbonate but delayed by magnesium oxide or aluminum hydroxide. Naproxen also is absorbed rectally, but more slowly than after oral administration. The half-life of naproxen in plasma is variable. It is about 14 hours in the young, but it may increase about twofold in the elderly because of age-related decline in renal function. 

It is a propionie acid structural analogue closely related to ibuprofen and naproxen. The mechanism of action most probably relates to its inhibition of prostaglandin synthesis. The drug gets rapidly absorbed after the oral administration. Peak plasma-levels (of about 50 meg. mL are attained within 2 hour after oral administration of a 600 mg dosage. The plasma half-life is nearly 3 hour. It is highly bound to albumin upto 90%. 

It is absorbed almost completely from the Gl-tract after an oral administration. Peak plasma levels (- 55 mg.mL are accomplished after 4 to 5 doses at an internal of 12 hours. It has been observed that more than 99% gets bound to serum albumin. The mean plasma half-life is nearly 13 hour. About 95% of a dose gets excreted in the urine, largely as conjugates of naproxen and its corresponding inactive metabolite 6-demethyl-naproxen. 

When administered as the acid or the sodium salt, naproxen is completely absorbed from the gastrointestinal tract the sodium sait is absorbed more rapidly than the acid (1). Peak plasma levels (about 55 (ig/ml) are reached in 2 to 4 hours after a 500 mg dose, and steady state ieveis are attained after 4-5 doses at 12 hours intervals. More than 99% is bound to serum albumin. The mean plasma half life is about 13 hours (2). Approximately 95% of a dose is excreted in the urine, principally as conjugates of naproxen and it s inactive metabolite 6-desmethyl naproxen (2). 

The apparent volume of distribution of naproxen averaged abut 8.3 L in healthy adults and about 11.9 L in patients with severe renal failure (serum creatinine 5.4-12.5 mg/dl)(2). In healthy adults, plasma half-life of naproxen reporfly ranges from 10-20 hours. 

Naproxen had no significant effect on the AUC, half-life, or clearance of methotrexate and its major metabolite 7-hydroxymethotrexate in 18 patients with rheumatoid arthritis given intravenous methotrexate 15 mg weekly. Other studies have found that naproxen did not affect the pharmacokinetics of methotrexate. In a study in 27 patients with rheumatoid arthritis who had taken oral methotrexate 7.5 to 15 mg weekly for at least 3 months, the concurrent use of naproxen 600 mg twice daily with lansoprazole did not affect the pharmacokinetics of methotrexate or 7-hydroxymethotrexate. Another study in patients with rheumatoid arthritis with normal renal function found that no toxicity was caused when naproxen 500 mg twice daily was given with methotrexate 15 mg given orally or intravenously, nor was the methotrexate clearance altered. ... 

Distribution naproxen has a volume of distribution of 0.16 L/kg. The elimination half-life of naproxen is approximately 15 hours following normal therapeutic doses. Naproxen is almost completely (99%) boimd to albumin and other plasma proteins. It crosses the placenta and appears in the milk of lactating women at approximately 1% of the plasma level concentration. Substantial amounts are found in the spinal fluid [1-3]. 

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