Mohammad A. Rashid

Prevalence of CYP2C19 alleles, pharmacokinetic and pharmacodynamic variation of clopidogrel and prasugrel in Bangladeshi population

The extent to which cytochrome P450 (CYP) 2C19 genotype influences the effectiveness of clopidogrel remains uncertain due to considerable heterogeneity between studies. We used the polymerase chain reaction restriction fragment length polymorphism (PCR‐RFLP) method for genotyping loss of function (LOF) allele, CYP2C19*2 and gain of function (GOF) allele, CYP2C19*17 in 163 patients undergoing PCI and 165 healthy volunteers from an ethnically distinctive Bangladeshi population. Thirty‐eight patients took prasugrel and 125 patients took clopidogrel among whom 30 patients had their clopidogrel active metabolites (CAM) determined by LC‐MS/MS 1–1.5 h after clopidogrel intake. All patients who underwent PCI had their P2Y12 per cent inhibition (PRI) measured by VerifyNow System. The impact of different genotypes on CAM and PRI were also determined. We did not find significant variation of CYP2C19*2 (P > 0.05) and CYP2C9*17 (P > 0.05) alleles among healthy volunteers and patients. CAM concentration as well as PRI by clopidogrel varied significantly (P < 0.05) based on genotypic variation of CYP2C19*2 and CYP2C19*17 individually. Such influence was not observed in case of prasugrel. Genotypic variation did not impact PRI but as a whole PRI by prasugrel was better than that of clopidogrel (P < 0.05). Due to presence of both of alleles the effect on PRI by clopidogrel could not be predicted, effectively indicating possible involvement of other factors. Genotype guided clopidogrel dose adjustment would be beneficial and therefore we propose mandatory genotyping before clopidogrel dosing. Prasugrel proved to be less affected by genotypic variability, but due to lack of sufficient long‐term toxicity data, caution would be adopted before substituting clopidogrel.

Evaluation of the Safety and Adverse Effects of Goreisan/Wulingsan, a Traditional Japanese-Chinese Herbal Formulation (Kampo), in a Rat Model: a Toxicological Evaluation

Diarrhea is the second leading cause of death among children less than 5 years of age. Most of these deaths occur in developing countries in the tropical areas of Africa and South Asia. Goreisan/Wulingsan, a formula of Japanese-Chinese medicinal herbs (Kampo), has been used for the treatment of diarrhea and vomiting from ancient times in East Asia. Therefore, we planned a randomized controlled clinical trial of Goreisan/Wulingsan in Bangladeshi children. Although it is believed to be safe in East Asia, information regarding its toxicity on animals is scarce. Since Goreisan/Wulingsan has never been used in Bangladesh, it was necessary to ensure the safety of the formula in an animal experiment. Rats were assigned to a control group (normal saline, n = 4) or various Goreisan/Wulingsan groups (n = 26) receiving doses of 1 to 8 mg/g/day (7.7 to 61.5 times the recommended pediatric dose) over a period of 25 days. Their activities and health conditions were observed until they were sacrificed, after which blood samples were collected for biochemical liver function tests. The kidneys, liver and heart tissue were collected for histopathological study. No lethality was observed during the experiment. All of the rats consumed the doses completely and no constipation was observed, suggesting the absence of any inhibitory effect on intestinal motion. Also, no abnormal neurological activity was detected, nor any significant elevation of AST, ALT or ALP levels, except for AST and ALT at the highest dose of 8 mg/g/day. Histopathological studies of the kidneys, liver and heart tissues revealed no abnormalities. In conclusion, our results showed that Goreisan/Wulingsan is safe for rats, thereby justifying the use of the drug in a human trial.

Interactive Pro-Adipogenic Effect of 15-deoxy-Δ12,14-Prostaglandin J2 to Interfere the Inducible Synthesis of Anti-Adipogenic Prostanoids in Cultured 3T3-L1 Preadipocytes, an Important Molecular Event to Consider for Drug Development

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka-1000, Bangladesh; Center for Integrated Research in Science, Shimane University; United Graduate School of Agricultural Sciences, Tottori University; Department of Life Science and Biotechnology, Faculty of Life and Environmental Science, Shimane University; Department of Clinical Pharmacy, Faculty of Pharmacy, Tokushima Bunri University

Recent Trends in Natural Product Research and Bangladesh Perspective

Background: Natural products, especially those derived from higher plants, have attracted scientists from ancient time because of their potential therapeutic values. Drug development from natural sources showed that natural products or natural productderived drugs comprised about 28% of all new chemical entities launched to the market. These are originated from terrestrial plants, microbes, marine organisms, etc. However, until recently an insignificant part of the plants has been scientifically evaluated for their medicinal properties. Bangladesh is a rich repository of medicinal plants, many of which are widely used in the Ayurvedic, Unani, herbal and other traditional systems of medicines. The study programs were initiated to investigate some of the traditionally used medicinal plants of Bangladesh, including Corypha taliera, the only living wild species of tali palm for the discovery of novel drug candidates as well as to isolate and identify bioactive compounds from several microbial strains and marine samples.