Naproxen elimination

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 order to determine more precisely the fate of pharmaceuticals during sludge treatment, different experiments have been conducted in controlled conditions. In continuous anaerobic reactors treating sludge spiked with pharmaceuticals, Carballa et al. [114] observed removals higher than 80% for naproxen, sulfamethoxazole, and roxithromycin, while 40% and 23% of ibuprofen and iopromide, respectively, were eliminated at both mesophilic (37°C) and thermophilic (55°C) temperatures. For diclofenac and diazepam, elimination of about 60% was observed in mesophilic conditions while in thermophilic conditions, 38% and 73% of these two compounds, respectively, were eliminated. In these experiments, the sludge retention time (15 or 30 days) did not seem to influence pharmaceutical removal... 

No detectable amounts of naproxen or its lysine conjugates were found in the plasma after administration of the conjugate and it can be inferred that excretion into the urine is the crucial process which determines the elimination rate fi. The lack of diffusion into the bloodstream is a favourable property in relation to unwanted extra-renal effects. 

Other drugs are metabolised by Phase II synthetic reactions, catalysed typically by non-microsomal enzymes. Processes include acetylation, sulphation, glycine conjugation and methylation. Phase II reactions may be affected less frequently by ageing. Thus according to some studies, the elimination of isoniazid, rifampicin (rifampin), paracetamol (acetaminophen), valproic acid, salicylate, indomethacin, lorazepam, oxazepam, and temazepam is not altered with age. However, other studies have demonstrated a reduction in metabolism of lorazepam, paracetamol (acetaminophen), ketoprofen, naproxen, morphine, free valproic acid, and salicylate, indicating that the effect of age on conjugation reactions is variable. 

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). 

Aspirin (now a generic name) is one of a number of nonsteroidal antiinflammatory drugs (NSAIDs) others include ibuprofen and naproxen (see Fig. 21-15), all now sold over the counter. Unfortunately, aspirin reduces but does not eliminate the side effects of salicylates. In some patients, aspirin itself can produce stomach bleeding, kidney failure, and, in extreme cases, death. New NSAIDs with the beneficial effects of aspirin but without its side effects would be medically valuable. 

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]. 

Biliary elimination of active forms (indometacin and sulindac) or no biliary elimination information available (naproxen). 

The nonsalicylate NSAIDs are especially useful for pain of inflammatory origin.These analgesics are relatively safe, are well tolerated, have few serious side effects, can decrease or even eliminate the need fc>r opioids, and are nonaddictive. NSAIDs that have been used effectively and are approved for use in children include ibuprofen, naproxen, and tolmetin. Because all these drugs can cause gastritis, they should be taken with meals. If GI side effects persist with one NSAID, an alternative agent should be selected. 

Total loads ranged from 2 to 5 g/day/1000 inhabitants in influent wastewaters and from 0.5 to 1.5 g/day/1000 inhabitants in effluent wastewaters. The average removal of ketoprofen, naproxen, ibuprofen, diclofenac and mefenamic acid in STPs was higher than 67 %, reaching values of >95 % in some cases. Lipid regulators, antihistaminics, antibiotics and /i-blockers were not so efficiently eliminated (average removal ranged... 

Describe the metabolism and elimination of naproxen and naproxen sodium. 

Eqn. (b) shows the interaction between (I) and two moles of ethyl-2-bromopropionate in the presence of THF, at 20°C for 24 hours followed by hydrolysis in the presence of metbanolic NaOH to yield the desired product naproxen with the elimination of one mole of CdBrg and two moles of ethanol. 

C. Pharmacokinetics. NSAIDs are generally well absorbed, and volumes of distribution (Vd) are relatively small (eg, 0.15 L/kg for ibuprofen). COX-2 inhibitors have larger volumes of distribution (86-91 L in adults for rofecoxib, 400 L for celecoxib). Most agents are highly protein bound, and most are eliminated through hepatic metabolism and renal excretion with variable half-lives (eg, 1.5-2.5 hours for ibuprofen and 12-17 hours for naproxen). (See also Table 11-59.)... 

Slattery JT, Levy G, Jain A, McMahon FG. Effect of naproxen on the kinetics of elimination and anticoagulant activity of a single dose of warfarin. Clin Pharmacol Ther (1979) 25, 51-... 

Reductive elimination forms tert-butyl naproxen, and regenerates the Pd° active catalyst (eq 6). 

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]. 

---