Value of therapeutic drug monitoring of endoxifen in Egyptian premenopausal patients with breast cancer given tamoxifen adjuvant therapy: A pilot study.

Background: The complex metabolic profile of tamoxifen anticancer drug and polymorphism in its metabolizing enzymes particularly CYP2D6 contribute to the high-observed inter-individual variability in its main active metabolite endoxifen. Therapeutic drug monitoring of endoxifen may play a key role in optimizing tamoxifen therapy, and control of both adverse effects and cancer recurrence. This pilot study aims to assess the clinical benefits of applying endoxifen measurement during tamoxifen therapy in patients with breast cancer.

Therapeutic Dilemma in Personalized Medicine.

The practice of medicine depends, over a long time, on identifying therapies that target an entire population. The increase in scientific knowledge over the years has led to the gradual change towards individualization and personalization of drug therapy. The hope of this change is to achieve a better clinical response to given medications and reduction of their adverse effects.

Deprescription in elderly: A spotlight on pharmacoeconomic aspect.

Aging is a complex process and many factors in the elderly, especially multiple diseases and related unnecessary drug use, support a deprescription approach to this age group to save money and health cost. In this review, we have searched for studies related to the pharmacoeconomic aspect of this deprescription approach in the elderly. Few studies are available, but they are promising and effective in paving the way for prospective longitudinal studies to assess the role of deprescription in optimizing the drugs prescribed to aged patients in a way that reduces the costs of both drug adverse effects and/or hospitalization.

The role of ITPA and ribavirin transporter genes polymorphisms in prediction of ribavirin-induced anaemia in chronic hepatitis C Egyptian patients.

Few data are available concerning the roles of polymorphisms of inosine triphosphatase (ITPA) gene and ribavirin (RBV) transporter genes in the prediction of RBV-induced anaemia among Egyptians with chronic hepatitis C (CHC). Genotyping of three ITPA gene variants and two variants of RBV transporter genes has been performed in 123 patients under pegylated interferon-α/ribavirin treatment. The baseline haemoglobin and ITPA rs1127354 CA/AA have been found as predictors of anaemia at 4, 8 and 12 weeks of RBV therapy.

Cardioprotective effect of atorvastatin alone or in combination with remote ischemic preconditioning on the biochemical changes induced by ischemic/reperfusion injury in a mutual prospective study with a clinical and experimental animal arm.

Background: Atorvastatin and remote ischemic preconditioning (RIPC) have beneficial cardiovascular protective effects. The aim of the study was to investigate possible effect of this drug alone and in combination with RIPC on the biochemical changes induced by ischemic/reperfusion injury (I/R) in a combined study with a clinical and experimental animal arm.

Methods: Thirty consecutive patients undergoing elective percutaneous coronary intervention (PCI) were divided into three groups (10 each): group I (control group without any preconditioning), group II (patients who were maintained on atorvastatin (80mg/day) for one month before PCI), and group III (similar to group II but PCI was preceded by RIPC).

Genetic variants in 6-mercaptopurine pathway as potential factors of hematological toxicity in acute lymphoblastic leukemia patients.

Aim: We investigated the associations between variants in genes coding for enzymes and transporters related to the 6-mercaptopurine pathway and clinical outcomes in pediatric patients with acute lymphoblastic leukemia.

Materials & Methods: Statistical association between gender, age and genotypes of selected SNPs, and the risks of hematological toxicity and relapse were investigated using a Cox proportional hazard model in 70 acute lymphoblastic leukemia patients from upper Egypt.

Results: We found significant associations between ITPA, IMPDH1, SLC29A1, SLC28A2, SLC28A3 and ABCC4 SNPs and one or more of the hematological toxicity manifestations (neutropenia, agranulocytosis and leukopenia); age was significantly related to relapse.

The AMPA receptor antagonist perampanel is a new hope in the treatment for epilepsy.

Perampanel is a novel drug recently approved as adjunctive therapy in epileptic patients aged 12 years and older who have drug-resistant partial epilepsy with and without secondary generalization. Pharmacological researches revealed that perampanel reduces neuronal excitability by a non-competitive antagonistic activity against the ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors causing modulation of glutamatergic neurotransmission. The pharmacological profile of the drug showed complete absorption following oral administration, and extensive metabolism in the liver by oxidation followed by glucuronidation with an elimination half-life of approximately 53-165 h (average: 105 h), allowing once-daily administration.

Drug therapy of heart failure: an immunologic view.

Heart failure (HF) is a clinical syndrome manifested by signs and symptoms of low cardiac output, pulmonary, and/or systemic congestion. Immunologically, HF is defined as a state of immune activation and persistent inflammation, especially the circulatory levels of inflammatory cytokines have been found to increase. Traditional drugs used in HF have expressed immunomodulatory and/or anticytokine activities that may participate in their therapeutic efficacy in the disease.

Variability in response to cardiovascular drugs.

Cardiovascular drugs are characterized by wide inter-individual variability in dose/plasma concentration/ response (therapeutic and/or toxic) relationships. Therefore, some patients achieve good therapeutic response to their drug therapy, while others do not. Also, some patients experience adverse effects, which vary from mild to life-threatening.

Pharmacokinetic-pharmacodynamic crisis in the elderly.

Aging is characterized by a progressive loss of functional capacities of most if not all organs, a reduction in homeostatic mechanisms, and a response to receptor stimulation. Also, loss of water content and an increase of fat content in the body are reported. Therefore, understanding the influence of age-dependent changes in composition and function of the body on the pharmacokinetics and pharmacodynamics of drugs is important before prescribing drugs to elderly patients.

Application of two-point assay of digoxin serum concentration in studying population pharmacokinetics in Egyptian pediatric patients with heart failure: does it make sense?

Digoxin pharmacokinetics (PK) was studied among a selected group of Egyptian pediatric patients (n = 40) with an age range of 0.33 to 15 years. All the patients had heart failure and were maintained on i.

NAT2*5/*5 genotype (341T>C) is a potential risk factor for schistosomiasis-associated bladder cancer in Egyptians.

Arylamine N-acetyl transferase (NAT2) displays extensive genetic polymorphisms that affect the rates of acetylation of drugs and genotoxic compounds such as amine carcinogens. To investigate whether the slow acetylator genotype is a risk factor for development of bladder cancer following schistosomal infection of the urinary tract, the authors determined the frequencies of 3 common polymorphisms in the NAT2 gene (341T>C, 590G>A, and 282C>T), which are associated with impaired acetylation activity, in control subjects (n=61; mean age 34.3+/-9.

Study of urinary 6 beta-hydroxycortisol/cortisol ratio in spot urine sample as a biomarker of 3A4 enzyme activity in healthy and epileptic subjects of Egyptian population.

The ratio of urinary 6 beta-hydroxycortisol/cortisol (6 beta-OHC/FC) in morning spot urine samples collected from 8:00 a.m. to 12:00 p.

Studying long-term effect of phenytoin either alone or combined with ascorbic acid on the anesthetic effect of urethane in rats.

Phenytoin is an anticonvulsant drug known to interact with many other drugs. Previous data suggest that chronic administration of phenytoin delays urethane-induced loss of righting reflex (LRR) and this phenomenon being potentiated by concomitant administration of ascorbic acid (ASC). Therefore, we examined how phenytoin at two different doses combined or not with ASC (fixed dose) interact with both the latency to, and the duration for urethane-induced LRR in experimental rats.

Pharmacokinetic modelling of valproic acid from routine clinical data in Egyptian epileptic patients.

Objective: This paper describes a developed pharmacokinetic model for the estimation of valproic acid (VPA) clearance (CL) calculated from routine clinical data taken from Egyptian epileptic patients.

Methods: Retrospective clinical data from 81 adult and paediatric epileptic patients with one trough VPA serum concentration per patient were analysed using NONMEM to estimate drug CL and determine the influence of different covariates. A qualification group of 20 epileptic children (3-13 years old) was used to evaluate the final model.

Therapeutic monitoring of digoxin and antiepileptic drugs in Egypt and Saudi Arabia.

Retrospective analysis was undertaken of serum drug levels determined in 1996 of 580 Egyptian and 1299 Saudi samples and in 2001 of 2361 Saudi samples. Monitored drugs were digoxin, carbamazepine, phenytoin, and valproic acid. The therapeutic drug monitoring results in 1996 showed no differences between the two countries in the rates of subtherapeutic, therapeutic, or toxic drug levels.

Population pharmacokinetics of digoxin in Egyptian pediatric patients: impact of one data point utilization.

A population pharmacokinetic (PK) study was designed to estimate the PK parameters of digoxin among a selected group of Egyptian pediatric patients (n = 30) with mean age +/- SD and body weight +/- SD of 8.88 +/- 3.01 years and 23.

Bayesian estimation of six different sets of carbamazepine pharmacokinetic parameters in Egyptian adult epileptic patients.

The individualization of carbamazepine (CBZ) dosage regimen based on estimation of pharmacokinetic (PK) parameters and measurement of serum drug concentration in epileptic patients can help to control epilepsy. In a retrospective study, the predictive performance of six different sets of CBZ PK parameters selected according to the literature was evaluated in 60 adult epileptic patients. Patients were administered controlled release CBZ (dose range: 200-1200 mg day(-1)) as monotherapy and one steady state serum concentration of the drug was available for each patient.