The purpose of the present review article is to update the information regarding pharmacokinetics of drugs in patients with heart failure that has accumulated since the last review article published in 1988 in Clinical Pharmacokinetics. Since this last review, our understanding of the pathophysiology of heart failure has changed from the cardio-renal model to the neuro-humoral model, and the pharmacologic approach to treatment of heart failure has been shifted from inotropic agents to those acting on the renin-angiotensin-aldosterone system. The pharmacologic agents now used for heart failure include many important classes of drugs, such as ACE inhibitors, angiotensin receptor blockers (antagonists) (ARBs), and mineralocorticoid receptor antagonists. In Part 1 of this review, we summarized the pharmacokinetic properties of relevant drugs administered intravenously. In Part 2, the present article, we describe pharmacokinetics of drugs following oral administration. For this purpose we conducted a systematic search of literature using MEDLINE, EMBASE, and Japan Centra Revuo Medicina (in Japanese). We retrieved a total of 110 relevant publications for 49 drugs and updated the information for ten drugs and provided new information for 31 drugs. We recognized that the pharmacokinetic data were obtained primarily from stable heart failure patients with moderate severity [New York Heart Association (NYHA) class II or III]. In addition, most patients were classified as heart failure with reduced ejection fraction. Furthermore, because most of the studies retrieved had no comparative groups of healthy subjects or patients without heart failure, historical controls from previous studies were used for comparisons. In Part 2, we also discuss the pharmacokinetics of active metabolites as well as parent drugs, because many drugs given by oral administration for the treatment of heart failure are prodrugs (e.g., ACE inhibitors and ARBs). The pharmacokinetic changes of drugs in patients with heart failure are discussed in the light of a physiologically based pharmacokinetic model. In addition, we discuss the effects of intestinal tissue heart failure-associated edema on drug absorption as it relates to the biopharmaceutical classification system, particularly for drugs demonstrating reduced systemic exposure as measured by the area under the plasma concentration-time curve after oral administration (AUCpo) in patients with heart failure as compared with healthy subjects. After review of the available data, it was seen that among patients with asymptomatic or compensated chronic heart failure there seemed to be no or minimal alterations in the maximum concentration (C max) and AUCpo of the included drugs, unless there was concurrent liver and/or renal dysfunction. In contrast, the AUCpo of at least 14 drugs (captopril, cilazaprilat, enalapril/enalaprilat, perindopril, carvedilol, candesartan, pilsicainide, felodipine, furosemide, enoximone, milrinone, flosequinan, molsidomine, and ibopamine) were suspected or documented to increa...

A literature review identified more than 150 unlabeled uses of IVIG. The evidence for these uses is being interpreted in different ways by various reviewing organizations.

The inhaled anesthetics have been shown to be both safe and effective in inducing and maintaining anesthesia. These agents differ in potency, adverse-effect profile, and cost. Newer anesthetic gases, such as sevoflurane and desflurane, appear to have more favorable physico-chemical properties. These factors, as well as patient characteristics and duration and type of procedure, must be considered when selecting an inhaled anesthetic.

Data for the use of metformin and topiramate in the treatment and prevention of second-generation antipsychotic-induced weight gain are limited. Both may be effective in helping patients lose weight via mechanisms that have yet to be clearly defined. The use of metformin results in greater weight loss than topiramate, and topiramate is associated with more risks and may compromise the treatment of schizophrenia. Treatment of antipsychotic-induced weight gain with metformin may be an option after lifestyle and dietary changes have failed.

Heart failure is one of the leading causes of death in developed countries, and its prevalence is expected to increase further in the coming years. While the pharmacokinetic changes observed in patients with heart failure have been reviewed twice in Clinical Pharmacokinetics, approximately a quarter century has passed since the latest article was published in 1988. Since then, many important classes of agents (e.g. ACE inhibitors, angiotensin receptor antagonists and inotropes) have been introduced for the treatment of heart failure. The aim of the present article is to update the information regarding the pharmacokinetics of these drugs. For this purpose we have made a systematic survey of literature using MEDLINE, EMBASE and Japan Centra Revuo Medicina (in Japanese) and found a total of 111 relevant publications for 58 drugs. Heart failure is a pathophysiological state where the damaged heart, from whatever causes, no longer pumps enough blood for the needs of body tissues at rest or during the normal daily activities. The spectrum of heart failure ranges from acute decompensated heart failure (including circulatory shock) to chronic compensated or decompensated heart failure. Because hypoperfusion of organs may influence drug absorption from the gastrointestinal tract, distribution into tissues and elimination either by the liver or kidneys, it is conceivable that the pharmacokinetics of many drugs may be altered in patients with heart failure. The pharmacokinetic changes of drugs in these patients in the light of a physiologically based pharmacokinetic model are discussed, since this model can interpret altered pharmacokinetics in terms of changes in the binding of drugs in plasma and tissue, blood flow to drug-eliminating organs and intrinsic activity of drug elimination. Pharmacokinetic changes of drugs after intravenous administration are described here in Part 1 and those after oral administration will be discussed in Part 2 in a later issue of the Clinical Pharmacokinetics. Reviewing the retrieved data, it was considered that patients with asymptomatic or compensated chronic heart failure seem to have no or minimal alterations in the pharmacokinetics of parenterally administered drugs as long as there was no concurrent liver and/or kidney dysfunction. In contrast, it was found that the systemic clearance of at least six drugs (i.e. milrinone, carperitide, molsidomine, theophylline, ciclosporin and hydralazine) was reduced after intravenous administration by 50 % or more in patients with acute decompensated heart failure or chronic severe heart failure (New York Heart Association class III or IV) as compared with healthy subjects. Because there is a paucity of information regarding the pharmacokinetics of drugs in patients with severe heart failure, close attention should be paid to monitoring the efficacy of these agents and their associated adverse effects.

Administration of factor products (factor VIII and recombinant factor VIIa) via continuous infusion has produced favorable hemostatic effects compared with intermittent bolus injections. The advantages of continuous infusion include maintenance of a constant factor concentration, thereby reducing risk of bleeding from excessively low trough concentrations, and a decrease in factor consumption related to a reduction in factor clearance with constant infusion. Manufacturers recommend using reconstituted factor products either immediately or within 1-3 hours after reconstitution; however, several studies have found the products to be stable and sterile for longer periods.

Atypical antipsychotics represent a treatment option for symptoms associated with autistic disorder. However, these drugs do not affect the core symptoms of autistic disorder and are associated with potentially significant adverse effects. In addition, there is a lack of randomized controlled trials to determine the true efficacy and long-term safety of these agents in the pediatric population.

Health care-acquired infections are a significant cause of morbidity and mortality in all patient care settings. In 2009, a consensus conference was held to evaluate practices and recommendations for the prevention and control of one specific type of health care-acquired infections, those associated with central catheter use. The conference had 2 purposes--to provide a tool for quality changes within health care institutions regarding central catheter infections and to empower those who are responsible for implementing policies needed to reduce the risk of these infections. The findings of the expert panel assembled for the conference are presented in this article.