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Drug Interaction Potential (drug + interaction_potential)

Distribution by Scientific Domains

Medical Sciences	60%
Chemistry	40%

Selected Abstracts

Role of drug metabolism in drug discovery and development

MEDICINAL RESEARCH REVIEWS, Issue 5 2001
Gondi N. Kumar
Abstract Metabolism by the host organism is one of the most important determinants of the pharmacokinetic profile of a drug. High metabolic lability usually leads to poor bioavailability and high clearance. Formation of active or toxic metabolites will have an impact on the pharmacological and toxicological outcomes. There is also potential for drug,drug interactions with coadministered drugs due to inhibition and/or induction of drug metabolism pathways. Hence, optimization of the metabolic liability and drug,drug interaction potential of the new chemical entities are some of the most important steps during the drug discovery process. The rate and site(s) of metabolism of new chemical entities by drug metabolizing enzymes are amenable to modulation by appropriate structural changes. Similarly, the potential for drug,drug interactions can also be minimized by appropriate structural modifications to the drug candidate. However, the optimization of the metabolic stability and drug,drug interaction potential during drug discovery stage has been largely by empirical methods and by trial and error. Recently, a lot of effort has been applied to develop predictive methods to aid the optimization process during drug discovery and development. This article reviews the role of drug metabolism in drug discovery and development. © 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 5, 397,411, 2001 [source]

Study on the pharmacokinetics drug,drug interaction potential of glycyrrhiza uralensis, a traditional Chinese medicine, with lidocaine in rats

PHYTOTHERAPY RESEARCH, Issue 5 2009
Jingcheng Tang
Abstract Drug,drug interaction potentials of an herbal medicine named Glycyrrhiza uralensis was investigated in rats via in vitro and in vivo pharmacokinetic studies. P450 levels and the metabolic rate of lidocaine in the liver microsomes prepared from different treatment groups were measured. In a separate in vivo pharmacokinetic study, the pharmacokinetic parameters of lidocaine in plasma and urine were estimated. P450 levels in the rats pretreated by Glycyrrhiza uralensis were significant higher than that in the non-treatment control. The increase in P450 levels was dose-dependent. Glycyrrhiza uralensis (1 and 3 g/kg) increased P450 levels by 62% and 91%, respectively, compared with the non-treatment control (0.695 nmol/mg protein). The metabolic rate of lidocaine in the liver microsomes was significantly higher in the herb pretreated rats. The pharmacokinetic profile of lidocaine was significantly modified in the rats with the herbal pretreatment. Elimination half-lives were shortened by 39%, and total clearances were increased by 59% with the pretreatment of Glycyrrhiza uralensis. In conclusion, Glycyrrhiza uralensis showed induction effect on P450 isozymes. Efficacy and safety profiles of a drug may be affected when the herbal products or herbal prescriptions containing the plant medicine were concomitantly used. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives

BIOMEDICAL CHROMATOGRAPHY, Issue 1 2010
Mullangi Ramesh
Abstract The introduction of irinotecan has revolutionized the applicability of camptothecins as predominant topoisomerase I inhibitor for anti-cancer therapy. The potent anti-tumor activity of irinotecan is due to rapid formation of an in vivo active metabolite, SN-38. Therefore, irinotecan is considered as a pro-drug to generate SN-38. Over the past decade, side-by-side with the clinical advancement of the use of irinotecan in the oncology field, a plethora of bioanalytical methods have been published to quantify irinotecan, SN-38 and other metabolites. Because of the availability of HPLC, LC-MS and LC-MS/MS methods, the pharmacokinetic profiling of irinotecan and its metabolites has been accomplished in multiple species, including cancer patients. The developed assays continue to find use in the optimization of newly designed delivery systems with regard to pharmacokinetics to promote safe and effective use of either irinotecan or SN-38. This review intends to: firstly, provide an exhaustive compilation of the published assays for irinotecan, SN-38 and other metabolite(s) of irinotecan, as applicable; secondly, to enumerate the validation parameters and applicable conclusions; and thirdly, provide some recent perspectives in the clinical pharmacology arena pertaining to efflux transporters, pediatric profiling, role of kidney function in defining toxicity, drug,drug interaction potential of irinotecan, etc. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Trends in use of herbal and nutritional supplements in cardiovascular patients

CLINICAL CARDIOLOGY, Issue 2 2004
Tomasz Stys M.D.
Abstract Background: Use of herbs and nutritional supplements (known as naturoceuticals) is increasing in the USA, with about 50% of Americans taking naturoceuticals and spending over $10 billion per year for them. This raises concerns regarding their use instead of proven therapies, their side effects, and drug interaction potential. Hypothesis: The study sought to characterize cardiology patients who used supplements and to examine whether their use was diagnosis or doctor dependent, whether it affected patients' compliance, and what supplements were used. Methods: In all, 187 patients attending our cardiology clinic were interviewed, examined, and followed for up to 1 year. The users and nonusers of naturoceuticals were compared. Results: Supplements were used in 106 patients (an average of 3.1 naturoceutical per patient). There were no significant differences in their use by gender, age, primary care doctor specialty, or cardiovascular medications prescribed (except for statins). Patients with a history of myocardial infarction, coronary revascularization, hyperlipidemia, and a family history of coronary artery disease were more likely to use the supplements. Average low-density lipoprotein (106 vs. 108 mg/dl), average blood pressure (132/77 vs. 138/78 mmHg), and average hemoglobin (Hb)A1c (8.7 vs. 7.7%) showed no statistically significant differences between users and nonusers. Patients most commonly took multivitamins, vitamin E, vitamin C, vitamin B, folate, garlic, calcium, coenzyme Q10, and gingko. Conclusion: This study indicates that naturoceutical use is widespread among cardiovascular patients and it is difficult to predict clinically who the users are. Fortunately, according to our limited compliance measures, it appears that the naturoceutical use has not affected patients' compliance with traditional medications. Also, possibly a detrimental interaction potential between traditional medications and naturoceuticals has been demonstrated. [source]