Sci. Pharm., Volume 74, Issue 1 (March 2006) – 5 articles , Pages 1-75

Artemether (ART) is an efficacious anti-malarial drug that also displays antischistosomal properties. Laboratory studies have found that ART curtails the development of schistosoma worms and thus prevents morbidity. Grapefruit juice was found to interact with various drugs that have been metabolized by a form of Cytochrome P450, CYP3A4, thus increasing the plasma drug concentration. This work aimed to study the effect of grapefruit juice when administered before infection with Schistosoma haematobium and/or treatment with ART on its anti-schistosomal activity. Golden hamsters were infected each with 300 S. haematobium cercariae and divided into 6 groups (A – F), as follows: Infected control (A); infected received grapefruit juice before infection (B); or received grapefruit juice before infection and treated with ART (200 mg/k) at 5,6 and 7 weeks post infection (WPI) (C); or for 3 successive doses at 12 WPI (D); infected treated with ART alone (200 mg/k) at 5,6 and 7 WPI (E); infected received grapefruit juice (0.5 ml) half an hour before treatment with ART (200 mg/k) at 5,6 and 7 WPI (co-administration) (F). All groups were sacrificed 14 WPI. Some parasitological, biochemical and histopathological estimations were done. Results revealed that, the highest percent of worm reduction was observed in-group F (94.2%) compared to group C,E & D (87.3%, 77.6% & 65.9% respectively). The level of ALT, GGT, urea, thiol, albumin and alkaline phosphatase tend to normalize in accordance with the parasitological results. Neither hepatic granuloma nor prominent histopathological changes could be detected in group F. A minimal number of granulomas (1-3/animal) was observed in group E; meanwhile, the least diameter and collagen content of hepatic S. haematobium granulomas were observed in group C (125.6±5.5 & 2.4±0.572 respectively). The results of the present study demonstrated that, co-administration of grapefruit juice just before treatment with ART at 5, 6& 7 WPI enhanced its anti-schistosomal activity and improved the histopathological changes. Full article

Mebeverine hydrochloride suppositories were prepared using Witepsol H15 suppository base. The effect of different concentrations of various enhancers (surfactants, amino acids and osmotic modifiers) on the drug release form the prepared suppositories was studied. The results showed that mebeverine hydrochloride suppositories containing Brij 35 (2%) and urea (10%) were superior to the other formulations containing the tested enhancers. These formulae showed the highest release rates (K = 0.083 ± 0.004 min^-1 and 0.111 ± 0.005 min^-1 , respectively) that followed first-order kinetics with t_50% of 8.35 ± 0.45 min and 6.24 ± 0.33 min, respectively. Therefore, these two formulae with the control suppositories were subjected to in vivo study in albino rabbits compared to the commercial Duspatalin^® tablets and intravenous injection. Higher C_max (1770.26 ± 165.46 ng.ml^-1) within shorter T_max (0.75 ± 0.20 h) was observed after rectal administration of the control suppositories compared to that of commercially available film-coated tablets (Duspatalin^® – 135 mg). A significant difference (p≤0.05) between the absolute bioavailability of Duspatalin^® tablets (27.09 ± 3.80%) and control suppositories (46.66 ± 1.72%) was detected. Statistically (p≤0.05), the mean residence time (MRT) after oral administration of Duspatalin^® tablets (3.16 ± 0.30 h) was significantly longer than that after the rectal administration of control suppositories (2.73 ± 0.30 h). suppositories containing 2% Brij 35 showed higher plasma levels of the drug (2766.11± 339.50 ng.ml^-1) with an absolute bioavailability of 70.50 ± 10.51% compared to 27.09 ± 3.80% for Duspatalin^® tablets.
Full article

The effect of the ethanolic extract of Elaeagnus angustifolia was tested on dispersed smooth muscle cells (SMC) of the guinea pigs. A slight contractile response was observed when SMC were treated with low concentrations of the extract. Pre-treatment of the SMC with ethanolic extract of E. angustifolia caused concentration dependent inhibition of acetylcholine-induced contractions of the SMC. Full article

The synthesis of certain N-aralkyl(1-aminomethylcyclohexyl) benzenamines 6a-i, N-(alkyloxymethyl or aralkyloxymethylcyclohexyl)-N-arylbenzenamines 9a-l and 1-(1-(aralkylphenylamino)cyclohexyl methoxy)-3-isopropylaminopropan-2-ols 11a-c has been accomplished. These compounds exhibited anticonvulsant activity. Compounds 9h, 9b and 11a at doses 0.06, 0.075 and 0.08 mmol/kg, respectively provoked maximal anticonvulsant potential against pentylenetetrazol (PTZ) induced seizures test compared with diphenylhydantoin (0.2 mmol/kg) and valproic acid (0.24mmol/kg). Full article