Use of DMPC and DSPC lipids for verapamil and naproxen permeability studies by PAMPA.

Verapamil and naproxen Parallel Artificial Membrane Permeability Assay (PAMPA) permeability was studied using lipids not yet reported for this model in order to facilitate the quantification of drug permeability. These lipids are 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and an equimolar mixture of DMPC/DSPC, both in the absence and in the presence of 33.3 mol% of cholesterol. PAMPA drug permeability using the lipids mentioned above was compared with lecithin-PC. The results show that verapamil permeability depends on the kind of lipid used, in the order DMPC > DMPC/DSPC > DSPC. The permeability of the drugs was between 1.3 and 3.5-times larger than those obtained in lecithin-PC for all the concentrations of the drug used. Naproxen shows similar permeability than verapamil; however, the permeability increased with respect to lecithin-PC only when DMPC and DMPC/DSPC were used. This behavior could be explained by a difference between the drug net charge at pH 7.4. On the other hand, in the presence of cholesterol, verapamil permeability increases in all lipid systems; however, the relative verapamil permeability respect to lecithin-PC did not show any significant increase. This result is likely due to the promoting effect of cholesterol, which is not able to compensate for the large increase in verapamil permeability observed in lecithin-PC. With respect to naproxen, its permeability value and relative permeability respect lecithin-PC not always increased in the presence of cholesterol. This result is probably attributed to the negative charge of naproxen rather than its molecular weight. The lipid systems studied have an advantage in drug permeability quantification, which is mainly related to the charge of the molecule and not to its molecular weight or to cholesterol used as an absorption promoter.

Occurrence and removal of selected micropollutants in a water treatment plant.

The levels of 14 micropollutants including nine pharmaceuticals, two pesticides, and three endocrine disruptors were measured in a water treatment plant (WTP) in Seoul, Korea. Among the measured micropollutants, 12 (excluding atrazine and triclocarban) were found in the influent and effluent from the WTP, at levels ranging from 2 to 482 ng L(-1). The removal efficiencies of the detected micropollutants in the WTP ranged from 6% to 100%. Among them diclofenac, acetaminophen, caffeine, carbamazepine, and 2,4-D were effectively removed (>80%). Metoprolol was unlikely to be removed (6%) in the WTP process. Concentrations of acetaminophen, metoprolol, ibuprofen, and naproxen were higher in winter, while levels of herbicides of 2,4-dichloro-phenoxyacetic acid (2,4-D) were higher in summer. Metoprolol was hardly removed in the water treatment process. Laboratory experiments showed that compounds with logKow>2.5 (especially bisphenol-A, 2,4-D, carbamazepine, triclocarban and 4-nonylphenol) were effectively removed by coagulation process, and adsorption effect increased in proportion with hydrophobicity of micropollutants and the turbidity of water. Sunlight photodegradation also effectively removed sulfamethoxazole, sulfamethazine, caffeine, diclofenac, ibuprofen, and acetaminophen, which are photosensitizes. Chlorination was relatively not effective for the removal of micropollutants due to the lower chlorine dosage (2 mg L(-1)), lower contact time (1h), and already lower levels of micropollutants at the chlorination stage at WTP. Our results imply that micropollutants during coagulation stage at WTP can be removed not only by coagulation itself, but also by adsorption to clay particle especially for high turbidity water, and by sunlight photodegradation in the areas open to the atmosphere.

Naproxen degradation test to monitor Trametes versicolor activity in solid-state bioremediation processes.

The white-rot fungus Trametes versicolor has been studied as a potential agent for the removal of environmental pollutants. For long-time solid-phase bioremediation systems a test is required to monitor the metabolic status of T. versicolor and its degradation capability at different stages. A biodegradation test based on the percentage of degradation of a spiked model pharmaceutical (anti-inflammatory naproxen) in 24 h (ND24) is proposed to monitor the removal of pharmaceuticals and personal care products in sewage sludge. ND24 is intended to act as a test complementary to ergosterol quantification as specific fungal biomarker, and laccase activity as extracellular oxidative capacity of T. versicolor. For samples collected over 45 d, ND24 values did not necessarily correlate with ergosterol or laccase amounts but in most cases, they were over 30% degradation, indicating that T. versicolor may be suitable for bioremediation of sewage sludge in the studied period.

Fate of the nonsteroidal anti-inflammatory drug naproxen in agricultural soil receiving liquid municipal biosolids.

Naproxen (2-(6-methoxy-2-naphthyl) propionic acid) is widely used for the treatment of pain and swelling associated with arthritis, gout, and other inflammatory conditions. Naproxen has been detected in municipal sewage outflows and in surface waters and could reach agricultural land through the application of municipal biosolids or reclaimed water. The persistence characteristics of naproxen in three agricultural soils were investigated. In laboratory microcosms of moist soil incubated at 30 degrees C, [O-14CH3]naproxen was rapidly and thoroughly mineralized to 14CO2 with comparable kinetics in a sandy loam soil, a loam soil, and a silt loam soil. Naproxen mineralization was responsive to soil temperature and soil moisture content, consistent with the primary mechanism of dissipation being biodegradation. Mineralization of naproxen was hastened by the addition of liquid municipal biosolids (LMBs) from a municipal sewage treatment plant that aerated this material. Naproxen was stable in autoclaved soils with or without addition of autoclaved LMBs, whereas naproxen was rapidly mineralized in sterile soil supplemented with nonsterile LMBs. An enrichment culture was obtained from aerobically digested LMBs in a mineral salts medium with naproxen as the sole source of carbon. The culture converted the parent compound to the corresponding naphthol, O-desmethyl naproxen. In summary, naproxen was rapidly removed from soil, with mesophilic aerobic biodegradation being the primary mechanism of dissipation. Microorganisms carried in biosolids enhanced naproxen dissipation in soil, with the initial mechanism of attack likely being O-demethylation. We conclude on this basis that naproxen in soils receiving biosolids would be readily biodegradable and, in the absence of preferential flow or runoff, pose little risk for contamination of adjacent water or crops.

Naproxen concentrations in plasma and synovial fluid and effects on prostanoid concentrations.

OBJECTIVE: To test the hypothesis that unbound concentrations of naproxen in synovial fluid (SF) and plasma (P) are equal over a drug dosage interval at steady state or after a single dose of drug. The relationship between plasma and SF concentrations of naproxen, respectively, and prostaglandin concentrations were also examined. METHODS: Paired, sequential, total, and unbound naproxen concentrations were determined in plasma and SF in 2 groups of 6 patients. A single dose group was given naproxen 500 mg. The chronic dose group was given 500 mg bd for 7 days before collection of blood and SF samples. The effect of naproxen on prostanoid production by clotting whole blood (thromboxane B2, TXB2) and in SF (PGE2, 6-keto-PGF1 alpha) was determined by radioimmunoassay. RESULTS: Average area under the curve (AUC) of unbound (U) naproxen concentrations against time in plasma and SF were the same over a dosage interval at steady state (ratio AUCU,SF/AUCU,P, 1.12 +/- 0.18; p = 0.108), but not after a single acute dose (AUCU,SF/AUCU,P, 1.34 +/- 0.32; p = 0.044). Data from the single dose study revealed that the mean (+/- SD) of the concentrations required for 50% inhibition (EC50) of platelet derived TXB2 by total naproxen was 7.7 +/- 4.4 micrograms/ml (n = 5) and for unbound drug 25.4 +/- 22.0 ng/ml (n = 5). SF prostanoid concentrations after both acute and chronic dosing were low, as expected, but temporal and dose relationships of prostanoid concentrations with SF naproxen could not be discerned. However, this may reflect study design. CONCLUSIONS: The AUC of unbound naproxen in SF and plasma were similar at steady state. Plasma concentrations correlated with inhibition of TXB2 generation by platelets. There was sustained depression of PG concentrations in SF beyond the time suggested by plasma drug concentrations.