Current Clinical Pharmacology - Volume 1, Issue 2, 2006

Programmed cell death also called apoptosis plays a pivotal role in many physiological and pathological conditions. In the multi-step process of drug development, a number of medications are being designed to target strategic checkpoints of the apoptotic cascade either to induce or to inhibit programmed cell death. Conceptually, the assessment of programmed cell death in response to various therapeutic interventions appe Read More

The Angiotensin II receptor blockers (ARBs) have been efficacious and safe drugs for the treatment of hypertension, heart failure, diabetic nephropathy and stroke from several short and long term clinical trials. The ARBs exert their effects through selective blockade of the angiotensin II (Ang-II) subtype 1 (AT1) receptor and quite possibly through stimulation by Ang-II of the unoccupied subtype 2 (AT2) receptor. The ARBs Read More

The potential marketplace for biotech-derived products from different bioprocess modifications looms large. However, there is the widespread view that, for biopharmaceuticals, the process makes the product. The current practice includes the physic-chemical and biological tests required to demonstrate structural equivalence of both products, the assessment of the potential impact of process changes on the biological qualit Read More

Grapefruit juice (GFJ) interacts with a number of drugs, and can alter pharmacokinetics parameters of the drugs. As for these interactions, most reports have focused on the elevation of drug bioavailability by GFJ, but a few recent reports have indicated that GFJ reduced the absorption of drugs not metabolized by cytochrome P450 (CYP). The predominant mechanisms of GFJ-drug interaction are thought to be due primarily Read More

Microdialysis has been developed during the last 25 years by several authors primarily to study brain function and changes in levels of endogenous compounds such as neurotransmitters or metabolites in different laboratory animals. However, in the last ten years microdialysis sampling has been introduced as a versatile technique in the clinical setting. Although, microdialysis sampling has been extensively used for metabolic Read More

Selecting, evaluating and applying biomarkers in drug discovery and exploratory drug development do substantially shorten the time to reach a critical decision point. Biomarkers are most useful in the early phase of clinical development when measurement of clinical endpoints or true surrogates may be too time-consuming or cumbersome to provide timely proof of principle or dose-ranging information. The use of bio Read More

In male Sprague-Dawley rat model of acute renal failure induced by uranyl nitrate (rat model of U-ARF), the expression of CYP2C11 decreased by 20% of control, whereas that of CYP2E1 and 3A1(23) increased 2-4 and 4 times, respectively, as compared with controls. The expressions of CYP1A2 and 2B1/2 were not changed by U-ARF. The mRNA level of CYP2E1 increased 3 times and that of CYP2C11 decreased to 25% of Read More

The diagnosis of drug-induced liver injury is often one of exclusion with initial suspicion based on circumstantial evidence. The natural history, characteristics and limitations of this exclusion process are revised. Also, the numerous published attribution algorithms for evaluation of drug-related liver abnormalities are described and their characteristics and differences are illustrated with true patients from our clinical expe Read More