Exploring the intraluminal behavior of an oral drug product in the human gastrointestinal (GI) tract remains challenging. Many in vivo techniques are available to investigate the impact of GI physiology on oral drug behavior in fasting state conditions. However, little is known about the intraluminal behavior of a drug in postprandial conditions. In a previous report, we described the mean solution and total concentrations of ibuprofen after oral administration of an immediate-release (IR) tablet in fed state conditions. In parallel, blood samples were taken to assess systemic concentrations. The purpose of this work was to statistically evaluate the impact of GI physiology (e.g., pH, contractile events) within and between individuals (intra and intersubject variability) for a total of 17 healthy subjects. In addition, a pharmacokinetic (PK) analysis was performed by noncompartmental analysis, and PK parameters were correlated with underlying physiological factors (pH, time to phase III contractions postdose) and study parameters (e.g., ingested amount of calories, coadministered water). Moreover, individual plasma profiles were deconvoluted to assess the fraction absorbed as a function of time, demonstrating the link between intraluminal and systemic behavior of the drug. The results demonstrated that the in vivo dissolution of ibuprofen depends on the present gastric pH and motility events at the time of administration. Both intraluminal factors were responsible for explaining 63% of plasma Cmax variability among all individuals. For the first time, an in-depth analysis was performed on a large data set derived from an aspiration/motility study, quantifying the impact of physiology on systemic behavior of an orally administered drug product in fed state conditions. The data obtained from this study will help us to develop an in vitro biorelevant dissolution approach and optimize in silico tools in order to predict the in vivo performance of orally administered drug products, especially in fed state conditions.

Current guidelines on the management of hip and knee osteoarthritis (OA) do not compare safety of treatment modalities. We therefore systematically reviewed 20 studies investigating mortality and serious complications of both medical and surgical treatments for hip and knee OA using PubMed, Scopus, Web of Knowledge and Google Scholar. Mortality was the highest for naproxen (hazard ratio (HR) = 3 (1.9, 4.6)) and lowest for total hip replacement (relative risk (RR) = 0.7 (0.7, 0.7)). Highest gastrointestinal complications were reported for diclofenac (odds ratio (OR) = 4.77 (3.94, 5.76)) and lowest for total knee replacement (HR = 0.6 (0.49, 0.75)). Ibuprofen had the highest renal complications (OR = 2.32 (1.45, 3.71)), whereas celecoxib had the highest cardiovascular risk (OR = 2.26 (1, 5.1)) and lowest was for tramadol (RR = 1.1 (0.87, 1.4)). Results show that medical management of hip and knee OA, particularly with non-steroidal anti-inflammatory drugs, may carry higher mortality compared to surgery. Careful consideration should be given to medical management taking into account known co-morbidities.

Micellar mobile phase was utilized for the separation and quantification of two antimicrobial mixtures with some analgesics that were found to augment their antimicrobial activity, namely; cefotaxime sodium (CFX) with ibuprofen (IBU) and naproxen (NPX) (mixture Ι), and azithromycin dihydrate (AZT) with diclofenac sodium (DIC) (mixture ΙΙ). Both mixtures were analyzed using a C18 column operated at 50 °C using a mobile phase composed of sodium dodecyl sulphate (SDS), an organic modifier; (1-propanol or acetonitrile), and 0.3% triethylamine (TEA), adjusting pH to the required value with 2 M orthro-phosphoric acid, accompanied with UV detection. The proposed method was subjected to full validation procedure and was applied to determine the concentration of the studied antibiotics in homogenized liver, kidney and heart rat tissue samples, with or without the co-administered non steroidal anti-inflammatory drugs.

An efficient sterically hindered C2-symmetric bifunctional tertiary amine-squaramide organocatalyst for the asymmetric Michael addition/hemiketalization domino reaction of kojic acid derivatives with β,γ-unsaturated α-ketoesters has been designed. Pharmacology-relevant functionalized 2,3,4,8-tetrahydropyrano[3,2-b]pyran derivatives were produced over the catalyst in as low as 1 mol% with up to 99% yield and 99% ee. The procedure is at least 30-fold scalable and the catalyst is readily reusable in the catalytic reaction via acid-base extraction. Acylation of the products with (S)- or rac-ibuprofen and with undec-10-enoic acid afforded the corresponding chiral esters containing two privileged pharmacophoric motifs.

In response to the shortage of water resources, multiple processes have been applied to turn wastewater secondary effluent (SE) into potable water. However, trace organic contaminants (TOrCs) and high concentrations of organic matter contained in SE pose a significant challenge to the reclamation. In this manuscript, combined UV-based and biofilm processes were used to treat the SE spiked with ibuprofen (IBU) and clofibric acid (CA). The efficiency of these sequential treatments was characterized in terms of changes in dissolved organic carbon (DOC), absorbance at 254 nm (A254), fluorescence excitation-emission matrix (FEEM), the concentration of IBU and CA, and molecular weight of SE. Parallel factor (PARAFAC) was applied as the analysis method for FEEM of the samples and two fluorescent components were successfully identified: humic-like substances (C1) and protein-like matter (C2). Large reductions in A254, C1, C2, IBU, and CA were observed during the UV-based processes, especially with the addition of H2O2. Nearly 50% of A254, 80% of the component C1 were decreased and almost complete removal of the component C2 and TOrCs was achieved by UV/2.0 mM H2O2 after 90-min treatment. During the oxidation processes, the formation of lower molecular weight (LMW) compounds was detected, and the biodegradability of the organic matters was greatly increased. Although no significant DOC reduction was obtained in UV-based processes, an obvious further DOC reduction (30~60%) was achieved by biofilm treatment following UV-based processes, especially after UV/H2O2 treatments. In the meantime, large amounts of LMW were removed in the biofilm treatment process. This manuscript provides an effective advanced treatment of SE for the removal of DOC and TOrCs, facilitating the wastewater reclamation.

Idiosyncratic drug-induced liver injury (iDILI) is the second-most-common cause of acute liver injury. When it is caused by ibuprofen, it is quite rare, especially when not accompanied by systemic signs or symptoms. A young female patient presented with an ibuprofen overdose suicide attempt and then developed an acute liver injury within a few days. Given its rarity, ibuprofen-induced iDILI was initially a secondary differential, but when her course did not improve as expected, she was quickly evaluated for liver transplant. She fully recovered without needing the transplant, but this case highlights the importance of not only early suspicion/detection but also early referral to a transplant hepatology service.

Thalidomide was originally developed to treat primary neurological and psychiatric diseases. There are reports of anticonvulsant effects of thalidomide in rats and antiepileptic effects in patients. Hence, thalidomide (100, 200 and 400 mg/kg) was herein administered to mice to evaluate possible protection against seizures induced by the systemic administration of neurotoxins: 10 mg/kg of 4-aminopyridine (4-AP), 90 mg/kg of pentylenetetrazol (PTZ), or 380 mg/kg of pilocarpine. The effect of an NO and COX inhibitor (7-NI and ibuprofen, respectively) was also examined. The results show that thalidomide (1) induces the typical sedative effects, (2) has no anticonvulsant effect in mice treated with 4-AP, and (3) has anticonvulsant effect (400 mg/kg) in mice treated with PTZ and pilocarpine. It was found that 7-NI has an anticonvulsant effect in the pilocarpine model and that thalidomide's effect is not enhanced by its presence. However, thalidomide (200 mg/kg) plus 7-NI or ibuprofen tend to have a toxic effect in PTZ model. On the other hand, the combination of thalidomide and 7-NI or ibuprofen protects against pilocarpine-induced seizures. In conclusion, thalidomide did not exert an anticonvulsant effect for clonic-tonic type convulsions (4-AP), but it did so for seizures induced by PTZ and pilocarpine (representing absence seizures and status epilepticus, respectively). NO and prostaglandins were involved in the convulsive process elicited by pilocarpine.