DARU Journal of Pharmaceutical Sciences
Year:2002 | Volume:10 | Issue:4|Papers Count:8

Acebutolol (AC) is a chiral l3-adrenergicblocking drug, which is used primarily in the treatment of hypertension. After oral administration of a racemic mixture of the drug a secondary peak is observed in plasma concentration-time profiles of both R and S-enantiomers of AC. In the present study the pharmacokinetics of AC enantiomers in rats after intraduodenal (ID) and intraileal (11) administration was investigated to inspect the generation of double peaks due to window absorption. Another possibility for the formation of double peak due to bile depletion in the gut lumen was investigated in male Sprague-Dawley rats. In a bile duct cannulated rat, the blood concentration-time profiles contained two peaks. The bioavailability after oral administration for R- and S-enantiomers of AC were 36% and 34% which increased to 47% and 46% following 11administration respectively. These values increased to 69% and 68% after ID administration. While following 11administration of the racemate, the double peak disappeared, it retained after ID administration. These results suggest that the double peak phenomenon observed after oral administration of AC is due to site dependent absorption of the drug.

Phannacokinetics of albendazole sulphone in three different single oral doses of albendazole (ABZ) (400, 800 & l200mg) in 10 healthy human volunteers in a double blind three-way crossover design. were studied. The serum levels of the main metabolites of ABZ (albendazole sulphoxide (ABZ-SO) and albendazole sulphone (ABZ-So2)) were analyzed by a modified high-pressure liquid chromatography method. For both metabolites, there were no significant differences in the biological half life, normalized serum peak concentration (Cmax/Dose) and time to reach peak concentration (Tmax). However apparent learance (Clp/F), apparent distribution volume (Vd/F), normalized area under the serum concentration- time curve (AUC/Dose) and normalized area under the first moment curve (AUMC/Dose) of albendazole metabolites were statistically different for various doses, resulting in substantially lower serum concentration and thereafter lower AUC/Dose and AUMC/Dose in higher doses. Ratios of pharmacokinetic parameters of ABZ-SO to those of ABZ-So2 were calculated and there were no significant differences for various ABZ doses. It is concluded that dose dependent pharmacokinetics of ABZ- So2 results from dose dependency of the pharmacokinetics of ABZ-SO, on the basis of a change in fraction of absorbed dose (F) as a result of slow and incomplete dissolution of the main drug in the GI tract. It is also concluded that in the subjects under study sulphonation of ABZ-SO was not dose dependent

The high mortality rate associated with significant bleeding from stress ulceration has promoted efforts to prevent this complication in critically ill patients. Gastric pH is a key factor in the pathogenesis of stress ulceration and maintaining a pH of 4 or greater reduces the risk for development of the gastric ulceration. Our aim was to compare effects of intravenous bolus administration and continuous intravenous infusion of ranitidine on gastric pH in critically ill patients at the intensive care unit (ICU). Twenty patients who met the inclusion criteria were entered this prospective, randomized, cross over study. A total of 1500 gastric pH measurement was obtained for each phase of the study. Continuous infusion of ranitidine maintained a gastric pH greater than 4 over a longer period than that of bolus administration (22.1 hrs vs. 14.2 hrs, respectively; P<0.001). The pH-monitoring device which was made locally, was comparable to a standard international device. This study showed that continuous infusion of ranitidine was more effective than administration of an equivalent dose of the drug by bolus in maintaining the appropriate gastric pH required for the prevention of stress ulceration.

The effect of propranolol and isoproterenol on the hydrolysis of 4- nitrophenylbutyrate (PNPB) by the purified human plasma cholinesterase was studied. During the hydrolysis of PNPB, enzyme obeyed to Michaelis-Menten model. Propranolol was found to be a competitive inhibitor, and isoproterenol yielded a complex inhibition pattern. It could be explained that the inhibitory effect of propranolol shows noncooperativity between subunits of human plasma cholinesterase upon binding of PNPB. In contrast, isoproternol inhibitory effects indicate more than one type of binding sites on this enzyme.

The effects of methanolic crude extracts of some medicinal plants, which are used in Iranian traditional medicine on RS322N (rad52) of the yeast strians of Saccaromyces cerevisiae were investigated, using agar diffusion method and the concentration which produced 12 mm inhibition zone (IC12) was determined. The RS322N IC12 for Dorema ammoniacum (oleogum resin), Bunium persicum (fruit) and Illicium verum (fruit) were 3.14, 5.58 and 5.27 mg/ml respectively. Based on these findings, oleogum resin of Dorema ammoniacum is a potential cytotoxicagent and a good candidate for further studies.

Water-distilled essential oil from aerial parts of Ferula ovina (Boiss.) Boiss. growing wild at the vegetative stage in Isfahan province Iran was analyzed by GC/MS. Forty-three compounds consisting 86.7% of the total components were identified in the oil which was obtained in 1.0% (v/w) yield. Among them, carvacrol (9.0%), alpha-pinene (8.2%), geranyl isovalerate (7.2%) and geranyl propionate (7.0%) were the major components.

Heliotropium/dissitiflorum Boiss. collected from Rud-e-Shur Tehran Province, Iran was investigated for Pyrrolizidine alkaloids (PAs). Four alkaloids namely: heliotrine I, heliotrine N-oxide II, europine III and 5'-deoxylasiocarpine IV were identified. The structures of all compounds were confirmed by spectroscopic methods.

Ginkgo biloba (GB) preparations are now among the leading herbal medicines that exert a broad spectrum of possible clinical applications. Several methods have been reported for quantification of ginkgolides of GB and its pharmaceutical preparations and the HPLC techniques are now considered to be the method of choice. However, most reported HPLC methods are not simple and their work-up procedure is inadequate. The present paper describes a simple and non-expensive method for extraction and determination of ginkgolides A and B in GB leaves and their phytopharmaceuticals. The method is based upon extraction of ginkgolides from aqueous solution by activated charcoal, followed by extraction with Methanol and injection of the Methanolic solution into chromatographic system. Ginkgolides were separated on an ODS column with a mobile phase of water-methanol (67:33 v/v) at a flow rate of 1.0 ml/min and were detected at 220 nm. The mean recoveries of ginkgolide A and B were 97 and 98.4%, respectively. This method is simple and can be used for routine analysis of GB extracts and phytopharmaceuticals preparations.