Drug Metabolism and Drug Interactions最新文献

Background: The hypoglycemic effect of antidiabetic drugs varies with change in the level of endogenous substances in the body in diseased states largely due to alteration in drug-serum albumin binding affinity. The aim of the present study was to understand and quantify this effect.

Methods: Quenching of intrinsic fluorescence of human serum albumin was used to monitor the competitive binding of antidiabetic drugs (gliclazide, glimepiride, glipizide and repaglinide) and bilirubin/hemin/chloride ions.

Results and conclusions: Bilirubin and hemin were bound at site I and site II in human serum albumin with association constants of the order of 105. The presence of bilirubin decreased the binding affinity of all the antidiabetic drugs. In the presence of hemin, the binding of gliclazide and glimepiride increased significantly, whereas that of glipizide and repaglinide decreased. The presence of chloride ions decreased the association constants of all drugs except glimepiride. More than 20% increase in the percentage of free drug was observed for gliclazide in the presence of bilirubin and for repaglinide in the presence of bilirubin and hemin. A large decrease was also observed in the percentage of free gliclazide in the presence of hemin, and free glimepiride in the presence of hemin and chloride ions. Competitive binding mechanism has also been proposed. Significant changes (increase/decrease) in the availability of free pharmacologically active antidiabetic drugs, observed in some cases, can result in fluctuations in the blood glucose level of diabetic patients. The effect, which varied with the nature of the drug and the competing substance, was relatively large for gliclazide and repaglinide compared to other drugs.

Background: Allometric exponents in population pharmacokinetic analysis are regularly used but the issue of fixing or estimating an allometric exponent remains controversial. The objective of the current analysis is to evaluate the performance of a body-weight-dependent allometric exponent (BDE) model of remifentanil.

Methods: The study was conducted in 34 patients (neonates to 17 years and 2.5 to 97 kg body weight) following a single intravenous (IV) infusion of remifentanil (5 μg/kg). A population pharmacokinetic approach was taken to describe drug clearance by the following BDE equation: CL=CLpop(BW/14.6 kg)L×BW(-M). Three allometric models were used to explore the impact of allometric exponents on the total clearance of remifentanil.

Results: All model-fitted structural, covariate, and statistical parameters were estimated with good to excellent precision (%RSE). However, on the basis of calculated Akaike weights (0.000 for model 1, 0.004 for model 2, and 0.996 for model 3), model 3 is the most robust model to describe individual clearance estimates.

Conclusions: The BDE model performed best for the estimation of remifentanil clearance and is realistic and of practical value. Further investigation should be conducted for such models.

Ayurvedic medicines are available in the market as over-the-counter products. Today people use prescription and nonprescription medicines along with Ayurvedic medicines for quick relief from ailments. In the ancient texts of Ayurveda, the concept of interactions with various examples of food interactions and food-drug interactions are mentioned. Recent studies and publications reported drug interactions of Ayurveda medicines and modern drugs. In the present review article, the concept of interactions mentioned in the Ayurvedic texts along with the examples of food interactions, food-drug interactions and the recent research work and publications indicating the interactions of the Ayurvedic drugs and drug interactions of Ayurvedic medicines and modern drugs are compiled. This will help the consumer of the prescription and nonprescription medicines with the Ayurvedic medicines to be cautious about the probable interactions.

Artemisia absinthium, also known as wormwood, is used widely as an herbal medicine. In this report, we introduce an 82-year-old Turkish woman who was treated with warfarin for atrial fibrillation and was hospitalized for gastrointestinal bleeding as a result of extremely elevated international normalized ratio (INR) after consumption of A. absinthium. Naranjo adverse drug reaction probability scale score was 6, which indicated a probable relationship between the patient's elevated INR and her concomitant use of wormwood and warfarin. Clinicians should be vigilant about potential dangers of herbal medicines taken with conventional drugs, and patients taking drugs with a narrow therapeutic index, such as warfarin, should be educated about avoiding consumption of herbal medicines.

Background: The aim of the study was to evaluate the incidence of medication error and to categorize medication error in the general medicine department of a tertiary hospital. Thus, the study aims to promote safety in medication use and ensure quality in the healthcare service by effective utilization of a clinical pharmacist. The study objective was to detect and categorize medication errors, to ensure rational drug use in the hospital, to make recommendations for doctors, nurses, and patients to promote safe use of medications.

Methods: The study was conducted in inpatients in the general medicine department of a 350-bed multispecialty tertiary care referral hospital located in South India. It is a prospective observational study where data were collected using a data collection form which included patient demographic details, drug details, and criteria for identifying errors, its categorization, and the details of drugs involved in errors. Complete details of patients and medications were recorded through a review of medication charts, reviewing prescriptions, visiting nursing stations and the pharmacy, and personal interviews with patients and bystanders. Collected details were then evaluated to detect the prescribing, administration, dispensing error and drug interactions and were then recorded, suggesting necessary steps to prevent recurrence of reported medication errors.

Results: The study was conducted in 311 patients, where 168 were males (54%) and 143 were females (46%). Out of 311 cases, 36 cases (11.57%) had at least one error. The total number of errors found was 67, among which administration errors (28.35%) were the most frequently occurring types of errors, which was followed by prescribing errors (22.38%), dispensing errors (8.9%) and drug interaction, patient errors and other types of errors collectively contributed to the remaining portion. A total of 2742 medications were prescribed to 106 patients and the average number of medications per patient was found to be 8.8. The involvement of a particular medication class to the medication errors showed that the antimicrobial agents were contributing a maximum of (26.8%), which was followed by cardiovascular agents (20.8%). In third place were nonsteroidal anti-inflammatory drugs (11.9%) followed very closely by central nervous system drugs and gastrointestinal drugs (7.4%). The total percentage of drug interaction was 40.29%. Most interactions were of moderate type belonging to category C of medication errors.

Conclusions: The study helps to assess the incidence of medication error and to categorize medication error. In the general medicine department, the majority of patients were geriatrics who are more prone to errors, thus guidelines for safe use of medications in geriatrics should be strictly implemented to prevent medication errors. Antimicrobials are the major class of drugs involved i

Background: The use of herbs with allopathic medicines increases the possibility of herb-drug interaction, which may either be beneficial or harmful. Therefore, the present study was undertaken to determine the interaction of glibenclamide, a sulfonylurea, with the aqueous extract of garlic (Allium sativum), an herb used widely as an antidiabetic agent.

Methods: The interaction was evaluated by an acute study, chronic study, oral glucose tolerance test, and body weight estimation in streptozotocin-induced diabetic rats. Glibenclamide was given orally at two different doses of 0.25 and 0.5 mg/kg, and A. sativum extract (ASE) was administered at the dose of 500 mg/kg. Blood glucose level and body weight estimation were carried out at various intervals.

Results: The hypoglycemic effect observed with combinations of glibenclamide and ASE was greater than either of the drug given alone. Combined treatments of glibenclamide and ASE resulted in higher increase in body weight than alone treatments.

Conclusions: We conclude that ASE shows a synergistic effect with glibenclamide. This could be important in reducing the dose of glibenclamide to achieve an enhanced therapeutic effect with minimal side effects.

Many clinical trials and data from scientific investigations have suggested the effects of statins on high-density lipoprotein (HDL) metabolism, besides their actions in reducing low-density lipoprotein (LDL) cholesterol. These actions have been proposed as important anti-atherogenic properties that contribute to the additional reduction of risk for cardiovascular diseases. The regulation of genes involved in the reverse cholesterol transport (RCT) is very complex and the modulation exerted by statin treatment is poorly understood. In this review, we discuss the molecular mechanisms underlying the modulation of genes controlling the RCT with special emphasis on the reported tissue-specific effects of statins. The statin modulation of genes participating in the different stages of RCT (cholesterol efflux from peripheral tissues, HDL metabolism in the plasma and internalization by the liver) has been summarized. Recent reports on novel mechanisms of regulation by microRNAs are also discussed.

The etiology of diverse patient responses to a given pharmaceutical treatment has eluded science for decades. Only during the last 10-15 years has our understanding of the interplay between genetics and pharmaceuticals advanced to the point that personalized medicine may optimize therapies for each individual patient. The primary goals of personalized medicine are identifying individuals at risk of developing disease to better prevent disease in the healthy population, accurately monitoring each patient's response to therapy and predicting recurrence in order to pre-empt it. This review gives an explanation of biomarkers and addresses their role in the diagnosis and surveillance of various cancers. It also addresses the challenges of developing novel therapies utilizing newly discovered biomarkers.

Background: One of the most recommended methods of systemic antibiotic administration in periodontics is the combination of amoxicillin and metronidazole, which has great inhibitory effect on periodontal pathogens. The aim of this study is to determine the local concentrations of these drugs in gingiva and compare its distribution in healthy and inflamed tissues.

Methods: The study population was selected from patients referred to our department. Fifteen subjects were referred for crown lengthening, and another 15 subjects required flap surgery because of severe periodontitis. All 30 patients received three doses of amoxicillin 500 mg plus metronidazole 250 mg before surgery. Tissue samples were gathered during surgery, and chemotherapy was continued for 7 days with 8-h intervals. After 7 days, during the second appointment, the next samples were collected. Samples were sent to the laboratory to determine the drug concentration with the use of high-performance liquid chromatography.

Results: Amoxicillin concentration in healthy gingival tissue was not detectable. The concentrations after 24 h and 7 days of administration were 25.9±4.1 and 124.8±18 μg/mL, respectively. The values for metronidazole were 28.86±1.7, 1.70±0.3, and 36.0±1.5 μg/mL.

Conclusions: The combination of systemic amoxicillin and metronidazole for 7 days has sufficient gingival connective tissue concentration much more than the minimum inhibitory concentration in healthy and inflamed tissue.

The human CYP2A gene subfamily consists of three members, CYP2A6, CYP2A7, and CYP2A13. The CYP2A6 gene is highly polymorphic with approximately 40 annotated allelic variants. Individuals homozygous for some of these alleles have a total lack of CYP2A6 activity. The CYP2A6 protein is most abundant in liver and is expressed, although at much lower levels, in some other tissues, especially nasal mucosa. CYP2A6 differs from other human liver CYP forms in that it participates in the metabolism of very few currently used drugs. The two most relevant substrates for CYP2A6 are coumarin and nicotine. Coumarin is the marker substance for determining CYP2A6 activity both in vitro and in vivo. Approximately 80% of a nicotine dose is eliminated by CYP2A6, and there is a clear link between CYP2A6 genotypes, smoking behavior, and lung cancer risk.