Home About us Contact
|
Home About us Contact | ||
|
|
||
Intra-patient Variability (intra-patient + variability)
Selected AbstractsA review of basal insulinsDIABETIC MEDICINE, Issue 11 2003Anthony H. Barnett Abstract Tight glycaemic control (ideally, HbA1c < 7%) is central to reducing the risk of long-term complications of diabetes. This approach, for both Type 1 and Type 2 diabetes, commonly involves the use of basal insulin, and must be achieved with minimal risk of hypoglycaemia (particularly nocturnal episodes). Indeed, concern around hypoglycaemia is a major barrier to achieving tight glycaemic control, and is a common problem with those protracted-acting insulins most frequently used in clinical practice for basal insulin supply. Other drawbacks include inter- and intra-patient variability that compromises dosing reproducibility and unsuitability for single daily dosing. New long-acting human insulin analogues with action profiles designed to overcome these problems are now available in clinical practice or are under evaluation in clinical trials. Clinical evidence suggests efficacy and safety advantages for these analogues over NPH insulin (the most commonly used basal insulin), and may bring closer the goal of tight glycaemic control in patients with diabetes. [source] Individualized population pharmacokinetic model with limited sampling for cyclosporine monitoring after liver transplantation in clinical practiceALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2007P. LANGERS Summary Background, We recently developed and validated limited sampling models (LSMs) for cyclosporine monitoring after orthotopic liver transplantation based on individualized population pharmacokinetic models with Bayesian modelling. Aim, To evaluate LSM in practice, and to seek optimal balance between benefit and discomfort. Methods, In 30 stable patients, more than 6 months after orthotopic liver transplantation, previously switched from trough- to 2 h post-dose (C2)-monitoring, we switched to 3-monthly LSM 0,1,2,3 h-monitoring. During 18 months we evaluated dose, creatinine clearance, calculated area under the curve, intra-patient pharmacokinetic variability and ability to assess systemic exposure by several previously validated LSMs. Results, Within patients, there was variability of cyclosporine-area under the curve with the same dose (CV of 15%). Compared to C2-monitoring, there was no significant difference in dose (P = 0.237), creatinine clearance (P = 0.071) and number of rejections. Some models showed excellent correlation and precision with LSM 0,1,2,3 h comparing area under the curves (0,2 h: r2 = 0.88; 0,1,3 h: r2 = 0.91; 0,2,3 h: r2 = 0.92, all P < 0.001) with no difference in advised dose. Conclusions, The limited sampling model, with only trough- and 2-h sampling, yields excellent accuracy and assesses systemic exposure much better than C2 with less bias and greater precision. Considering the calculated intra-patient variability, more precision is redundant, so LSM 0,2 h seems the optimal way of cyclosporine-monitoring. [source] Prolongation of the prothrombin time and activated partial thromboplastin time in children with sickle cell diseasePEDIATRIC BLOOD & CANCER, Issue 5 2006Leslie J. Raffini MD Abstract Background Patients with sickle cell disease (SCD) have high rates of perioperative complications, including bleeding 1,2. Procedures We conducted a retrospective review of pre-operative coagulation studies in pediatric patients with SCD followed by a prospective study of 100 well children with SCD to determine the prevalence of abnormal coagulation screening tests, and to evaluate potential etiologies. Results In the retrospective study, 32/84 (38.1%) had a prolonged prothrombin time (PT), compared to 8/100 in the prospective study. Prolongations of the activated partial thromboplastin time (aPTT) were less common. Children in the prospective study with prolonged PTs had significantly lower levels of Factor V and VII compared to those with normal PTs. Factor VII levels were <50% in 4/8 with long PTs, compared to 3/92 with normal PTs, P,=,0.001. Though retrospectively, several patients had normalization of their PT with vitamin K, there was no laboratory evidence of vitamin K deficiency in the prospective study. In the retrospective analysis, six of seven children who had pre-operative coagulation studies and significant intraoperative blood loss had prolonged PTs (P,=,0.04). Conclusions Children with SCD admitted for surgical procedures were more likely to have prolonged PTs than those tested at a well visit. There was intra-patient variability in coagulation studies that may be related to clinical status, hepatocellular dysfunction, and/or increased clotting factor consumption. Future well-designed prospective studies to determine whether abnormal coagulation studies are associated with an increased risk of perioperative bleeding in children with SCD are necessary. Pediatr Blood Cancer 2006; 47:589,593. © 2005 Wiley-Liss, Inc. [source] High flow nasal cannula therapy as respiratory support in the preterm infant,PEDIATRIC PULMONOLOGY, Issue 7 2009Carlo Dani MD Abstract We reviewed the literature on the effects of high flow nasal cannula (HFNC) and heated, humidified, high-flow, nasal cannula (HHHFNC) treatment in preterm infants. We found nine studies, but only two were randomized controlled trials. These studies show that: HFNC application is associated to the delivery of continuous distending pressure (CDP) in patients with closed mouth, whose value is proportional to the delivered flow only in smaller infants; the CDP delivered by HFNC is unpredictable and present large inter-patient and intra-patient variability; the use of recently available HHHFNC devices is effective in minimizing nasal mucosa injuries compared to traditional HFNC; the effectiveness of HHHFNC versus NCPAP for the treatment of apnoea of prematurity, respiratory distress syndrome, and the prevention of extubation failure, has been poor investigated and firm conclusions cannot be drawn on this matter. In conclusion, on the basis of published data, the routinary application of HFNC should be limited to patients requiring oxygen-therapy, HHHFNC devices should be preferred to HFNC, but their employment as an alternative to NCPAP should wait for the conclusion of randomized controlled trials. Pediatr Pulmonol. 2009; 44:629,634. © 2009 Wiley-Liss, Inc. [source] Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiologyBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2010Adam L. VanWert Abstract Our understanding of the mechanisms behind inter- and intra-patient variability in drug response is inadequate. Advances in the cytochrome P450 drug metabolizing enzyme field have been remarkable, but those in the drug transporter field have trailed behind. Currently, however, interest in carrier-mediated disposition of pharmacotherapeutics is on a substantial uprise. This is exemplified by the 2006 FDA guidance statement directed to the pharmaceutical industry. The guidance recommended that industry ascertain whether novel drug entities interact with transporters. This suggestion likely stems from the observation that several novel cloned transporters contribute significantly to the disposition of various approved drugs. Many drugs bear anionic functional groups, and thus interact with organic anion transporters (OATs). Collectively, these transporters are nearly ubiquitously expressed in barrier epithelia. Moreover, several reports indicate that OATs are subject to diverse forms of regulation, much like drug metabolizing enzymes and receptors. Thus, critical to furthering our understanding of patient- and condition-specific responses to pharmacotherapy is the complete characterization of OAT interactions with drugs and regulatory factors. This review provides the reader with a comprehensive account of the function and substrate profile of cloned OATs. In addition, a major focus of this review is on the regulation of OATs including the impact of transcriptional and epigenetic factors, phosphorylation, hormones and gender. Copyright © 2009 John Wiley & Sons, Ltd. [source] | ||||||||||