Naproxen absorption

With respect to concomitant antacid administration past studies have shown that sodium bicarbonate enhances the rate of naproxen absorption, magnesium carbonate caused a slight reduction, and a mixture of magnesium oxide and aluminium hydroxide gave a clear reduction in the rate of naproxen absorption (17). 

Sodium bicarbonate increased the rate of naproxen absorption, and aluminium hydroxide and magnesium oxide decreased it. Dimeticone did not affect ketoprofen bioavailability. 

The strategy for the development of the oral absorption model at pION is illustrated in Fig. 7.58. The human jejunal permeabilities reported by Winiwarter et al. [56] were selected as the in vivo target to simulate by the in vitro model. In particular, three acids, three bases and two nonionized molecules studied by the University of Uppsala group were selected as probes, as shown in Fig. 7.58. They are listed in the descending order of permeabilities in Fig. 7.58. Most peculiar in the ordering is that naproxen, ketoprofen, and piroxicam are at the top of the list, yet these three acids are ionized under in vivo pH conditions and have lipophilicity (log Kj) values near or below zero. The most lipophilic molecules tested, verapamil and carbamazepine... 

FIGURE 17.11 ln uence of formulation on absorption of naproxen (500 mg) in humans (fed) mean plasma data from clinical trials = 23). Plasma levels of naproxen (mg/mL) are plotted as a function of time (h) where ( ) is Naproxen NanoCrys fedispersion, (0) is Naprox suspension, ancDO is Anapro tablet. 

Liversidge, G G. and Conzentino, P. (1995) Drug particle size reduction for decreasing gastric irritancy and enhancing absorption of naproxen in rite, J. Pharm., 125(2) 309-313. 

While many aspects of nonlinear pharmacokinetic behavior may impact on the above equation, the more relevant pharmacokinetic processes for ASOs are absorption and distribution at or below therapeutic or nontoxic plasma concentrations. Nonlinear absorption or distribution processes can affect AUC terms in a nonproportional manner when different doses are compared, thereby resulting in an inaccurate determination of bioavailability. This has been shown to occur on numerous occasions for compounds such as ascorbic acid or naproxen [59-62]. Such cases require an understanding of the capacity-limiting cause of the nonlinearity and the pharmacokinetic processes upon which this impacts, in case of ASOs absorption and intercompartmental distribution processes from the central compartment into the peripheral tissues. With this understanding, various methods may then be applied to best approximate the rate of change of the plasma concentrations from one sampling time to the next allowing for an estimate of the absolute BAV. 

The conjugates of arylpropionic acids enantiomers with D-glucuronic add were separated on a Beckman Ultrasphere ODS column (4.6 mm x 250 mm, 5 / m) column. The mobile phase was a 28 72 (v/v) mixture of acetonitrile and 8 mM tetrabutylammonium hydrogen sulfate buffer (pH 2.5). Five minutes after the diastereomeric conjugates had been resolved, the percentage of acetonitrile was increased to 60% to wash out excess substrate. The mode of detection depended on the samples injected. Fluorescence was used for flunoxaprofen (excitation, 305 nm emission, 355 nm), benoxaprofen (313/ 365 nm) carprofen (285/350 nm), and idoprofen (275/433 nm). UV absorption was used to detect flurbiprofen (255 nm), naproxen (285 nm), ketoprofen (255 nm), pirprofen (265 nm), and cicloprofen (238 nm). 

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]. 

Colestyramine Naproxen and probably other NSAIDs The anion exchange resin binds NSAIDs in gut, reducing the rate ( and extent) of absorption Separate dosing times by 4 hours may need higher than expected dosages of NSAIDs... 

Chowhan ZT, Pritchard R. Effect of surfactants on percutaneous absorption of naproxen I comparisons of rabbit, rat, and human excised skin. J Pharm Sci 1978 67 1272-1274. 

More recently, thymol has been shown to enhance the in vitro percutaneous absorption of a number of drugs, including 5-fluorouracil, piroxicam, propranolol, naproxen, and tamoxifen. Studies have also demonstrated that the melting point of lidocaine is significantly lowered when it is mixed with thymol. ... 

Figure 33-1 5 Typical separation by MECC. (a) Some test compounds 1 = methanol, 2 = resorcinol, 3 = phenol, 4 = p-nitroaniline, 5 = nitrobenzene, 6 = toluene, 7 = 2-naphthol, 8 = Sudan III capillary, 50-p.m inside diameter, 500 mm to the detector applied voltage, ca. 15 kV detection UV absorption at 210 nm. (b) Analysis of a cold medicine 1 = acetaminophen, 2 = caffeine, 3 = sulpyrine, 4 = naproxen, 5 = guaiphenesin, 10 = noscapine, 11 = chloropheniramine and tipepidine applied voltage, 20 kV capillary, as in (a) detection UV absorption at 220 nm. (From S. Terabe, Trends Anal. Client., 1989,8, 129.)...

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. ... 

Figure 2.10 Transient absorption spectra obtained on laser flash photolysis at 266 nm of naproxen (0.1 mM, pH 7.0). The spectra were recorded 0.02 ( ), 0.26 (o), and 1.29 psec ( ) after the flash. (From Moore, D.E. and Chappuis, P.P., Photochem. Photobiol., 47 173-181, 1988.)...

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. 

Warfarin reduces the synthesis of prothrombin and several other clotting factors. Carbamazepine and rifampin interfere with this action by increasing the metabolism of warfarin. Cholestyramine decreases the oral absorption of warfarin and other acidic drugs. Vitamin K is the antidote to excessive effects of warfarin. Antiplatelet drugs such as naproxen enhance the anticoagulant effects of warfarin. The answer is (C). 

Clinical trials have shown that raloxifene, in combination with oral calcium supplementation, decreases the risk of vertebral fracture and promotes bone formation, albeit to a lesser extent than with estrogen. Raloxifene has been shown to have a beneficial effect on lipid profiles (11). Raloxifene should not be administered in combination with cholestyramine (decreased absorption), coumadin (prothrombin times and international normalized ratios must be monitored more closely), and those drugs that are highly protein bound, such as clofibrate, diazepam, ibuprofen, indomethacin, and naproxen. 

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