Abstract: Objective: Rheumatoid arthritis (RA) is a common inflammatory disease associated with many extra-articular features. The aim of the study was to evaluate the effects of pentoxifylline (PTX) as adjuvant therapy to etanercept in moderately to highly active RA. Methods: A single center randomized double-blind placebo-controlled trial of 8 weeks duration was performed. Disease activity was measured via calculating the disease activity score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) and by simplified disease activity score in 28 joints using hsCRP (SDAI-CRP). 40 Patients who were using etanercept (ETN) were randomly allocated to receive each day either pentoxifylline 400mg tablet twice daily or capsules prefilled with glucose as placebo also twice daily and were evaluated at baseline and at week 8 for clinical and hematological parameters. Results: Tumor necrosis factor (TNF), high sensitive C-reactive protein (hsCRP), duration of morning stiffness, and cardiovascular risk were significantly more reduced in pentoxifylline group than placebo group after 8weeks. Non significant changes were observed in clinical parameter like swelling joints counts (SJC),tender joints counts(TJC),visual analogue scale(VAS),evaluator global assessment (EGA),DAS28-ESR, SDAI-CRP and hematological parameter like hemoglobin (Hb) amount, erythrocyte sedimentation rate (ESR) and white blood cells (WBC) count between groups. Conclusion: PTX significantly decreased pro-inflammatory markers (TNF, hsCRP), duration of morning stiffness and cardiovascular risk. This suggests that pentoxifylline may be a promising and useful strategy to reduce the systemic inflammation and cardiovascular morbidity and mortality observed in RA patients.

Abstract: It is generally recognized that poor solubility is one of the most frequently encountered difficulties in the field of pharmaceutics. Low solubility and subsequent unsatisfactory dissolution rate often compromise oral bioavailability. There are most therapeutic agents used to produce systemic effects by oral route that are the preferred way of administration owing to its several advantages and high patient compliance compared to other routes. However, poorly water-soluble drugs, when administered orally, have been shown to be slowly and unpredictably absorbed since their bioavailability is largely dependent on the dissolution process in gastrointestinal tract. This article demonstrates the various methods used to increase dissolution rates, preparation techniques of solid dispersion, and characterization methods of the solid dispersion.

Abstract: Indomethacin, in combination with prochlorperazine and caffeine (IPC), is often overused by migraine patients who develop medication-overuse headache. Indomethacin clearance is slower in chronic migraine patients overusing IPC combination than in migraine patients only occasionally taking it. The objective of this study was to verify if indomethacin reduced clearance reverted to normal values after withdrawal of the overused IPC combination. Therefore, we repeated the study of indomethacin pharmacokinetics in 9 female chronic migraine patients after 3 months from inpatient withdrawal treatment from IPC combination overuse. The IPC combination (indomethacin 50 mg, prochlorperazine 8 mg, caffeine 150 mg) habitually taken was administered by rectal route to each patient. Blood samples were drawn before dosing and at the following post-dose times: 0.5, 1, 2, 3, 4, and 6 h. Indomethacin concentrations were measured by HPLC method. We found that 4 of 9 patients (group A) who were still overusing the combination and suffering from daily headache had still high indomethacin concentrations after 6 hours, therefore showing a slow elimination of the drug. Instead, in the 5 patients (group B) who had discontinued overuse of IPC combination after withdrawal treatment, indomethacin concentrations after 6 hours were significantly lower than those measured before withdrawal (P < 0.05, Student’s t-test for paired data), and also than those observed in group A (P < 0.05, ANOVA and Newman-Keuls’test). Hence, by suspending IPC abuse indomethacin clearance reverts to normal values and this is associated with an improvement of migraine. Instead, the higher plasma levels of indomethacin in patients who continue IPC abuse do not solve migraine and might support medication-overuse headache.

Abstract: Here Benzimidazole analogues have been used to correlate the inhibition activity with the Eccentric Connectivity index (ECI), Fragment Complexity (FC) and McGowan Volumes (MG) descriptors for studying the quantitative structure activity relationship (QSAR) against methionine aminopeptidases for the development and evaluation of anti-cancer agents. Correlation may be an adequate predictive model which can help to provide guidance in designing and subsequently yielding greatly specific compounds that may have reduced side effects and improved pharmacological activities. We have used Multiple Linear Regression (MLR) for developing QSAR model. For the validation of the developed QSAR model, statistical analysis such as cross validation test (LOO-CV), quality factor, fischers test, root mean square deviation (RMSD), variance, standard deviation etc.; have been performed and all the tests validated this QSAR model with fraction of variance r² = 0.8906 and LOO-CV q² = 0.8904.

Abstract: Many flavonoids have the capacity to modulate the activity of drug metabolizing enzymes and transporters, thus raising the potential for alterations in the pharmacokinetics of drugs and other essential elements. The present study evaluates the effect of single supraphysiological orally administered doses of silibinin, epigallocatechin gallate (EGCG), quercetin and rutin on the absorption and tissue distribution of orally administered doses of the trace elements zinc copper and iron in rats. Thirty rats were allocated into 5 groups treated as follow: 1^st group treated with olive oil, served as control; the other 4 groups were administered orally single doses of either silibinin, EPGC, quercetin or rutin, after 2 hr a solution contains sulphate salts of zinc, copper and iron was administered orally. The animals were sacrificed, blood samples, tissues of brain, kidney and liver were obtained for evaluation of the plasma and tissues concentrations of Zn, Cu and Fe using atomic absorption spectrometry. All four flavonoids decreased serum and tissues concentrations of the trace elements compared with control. In conclusion, concomitant administration of single doses of Zn, Cu and Fe with supra-physiological doses of the flavonoids silibinin, EGCG, quercetin and rutin significantly decreases serum and tissue levels of these trace elements.