Bioequivalence study of rabeprazole sodium on healthy human volunteers.

The newly developed proton pump inhibitor rabeprazole sodium is expected to have beneficial effects in the treatment of peptic ulcer. The pharmacokinetic parameters (C(max), AUC(o-t), t(max)) of this drug have been evaluated to compare the single dose (20 mg) bioavailability of rabeprazole sodium with the standard reference. High performance liquid chromatography (HPLC) coupled with UV detector set at 280 nm has been used to determine plasma concentration of 12 human volunteers as per Drugs Controller General of India (DCGI) guidelines. The method has been validated over a linear range of 20-480 ng/ml from plasma. The minimum quantifiable concentration was set at 10 ng/ml [co-efficient of variance (CV) < 10%]. By comparing AUC(o-t) the relative bioavailability of test preparation has been found to be 100.88% of that of reference preparation.

Topoisomerase II poisoning by indazole and imidazole complexes of ruthenium.

Trans-imidazolium (bis imidazole) tetrachloro ruthenate (RuIm) and trans-indazolium (bis indazole) tetrachloro ruthenate (RuInd) are ruthenium coordination complexes, which were first synthesized and exploited for their anticancer activity. These molecules constitute two of the few most effective anticancer ruthenium compounds. The clinical use of these compounds however was hindered due to toxic side effects on the human body. Our present study on topoisomerase II poisoning by these compounds shows that they effectively poison the activity of topoisomerase II by forming a ternary cleavage complex of DNA, drug and topoisomerase II. The thymidine incorporation assays show that the inhibition of cancer cell proliferation correlates with topoisomerase II poisoning. The present study on topoisomerase II poisoning by these two compounds opens a new avenue for renewing further research on these compounds. This is because they could be effective lead candidates for the development of more potent and less toxic ruthenium containing topoisomerase II poisons. Specificity of action on this molecular target may reduce the toxic effects of these ruthenium-containing molecules and thus improve their therapeutic index.

ATP diphosphohydrolases: an overview

This review aimed at discussing the protocols used to characterize and to distinguish ATP diphosphohydrolases from other enzymes which can promote the degradation of ATP and ADP, since there is a confusion about the identily of this enzyme and ATPases.

Effect of anthelmintics and phenothiazines on adenosine 5'-triphosphatases of filarial parasite Setaria cervi.

S. cervi showed particulate bound Ca2+ ATPase and Na+,K(+)-ATPase activities while Mg2+ ATPase was detected in traces. ATPase of S. cervi was also differentiated from the nonspecific p-nitrophenyl phosphatase activity. Female parasite and microfilariae exhibited higher Ca2+ ATPase and Na+,K(+)-ATPase activities than the male adults and the enzyme Na+,K(+)-ATPase was mainly concentrated in the gastrointestinal tract of the filarial parasite. Na+,K(+)-ATPase of the filariid was ouabain-sensitive while Ca2(+)-ATPase activity was regulated by concentration of Ca2+ ions and inhibited by EGTA. Phenothiazines, viz. trifluoperazine, promethazine and chlorpromazine caused significant inhibition of Ca2+ ATPase and Na+,K(+)-ATPase. Diethylcarbamazine was a potent inhibitor of these ATPases. Mebendazole, levamisole and centperazine also caused significant inhibition of the ATPases indicating this enzyme system as a common target for the action of anthelmintic drugs.

Adenosine triphosphatase systems in genital tract of testosterone treated male adult monkeys.

Studies on the distribution of Na+, K+-dependent, Mg2+ dependent and Ca2+ dependent Adenosine Triphosphatase (ATP-ases) in the testes, epididymis, seminal vesicles and prostate glands of mature bonnet monkeys were carried out with and without Testosterone propionate (TP) treatment. Comparatively, the Ca2+ dependent ATP-ase was very active in the testes, caput and cauda epididymis and prostate of control animals. However, the Mg2+-dependent ATP-ase activity was predominant in the seminal vesicles. In all the genital tissues the Na+, K+ dependent ATP-ase exhibited low activity compared to other ATP-ase systems. On TP treatment at 1 mg/kg body wt. dose for 30 consecutive days to the second group of animals, all classes of ATP-ases drastically decreased in the testes, cauda epididymis, seminal vesicles and prostate. While in caput epididymis the Mg2+-dependent ATP-ase was stimulated, the Na+, K+-dependent ATP-ase was decreased both in the caput and corpus epididymis by the hormone treatment. The present study reveals the general inhibitory influence on the ATP-ase systems and thereby ionic transport after long term TP administration.