Objective: Computer-prescriber order entry (CPOE) systems that lack clinical decision components actually increase errors and cause harm rather than the opposite. Recent studies have also demonstrated that dosing errors, typing errors, or miscommunication with other systems are the most common CPOE errors. Our objective was to develop an antibiotic dosing ...

Abstract Objective. To investigate whether the increase in the number of doses of penicillin V from three times daily to four times daily for common infections, as recommended in the new Norwegian guidelines for antibiotic treatment in primary health care, would lead to reduced patient compliance. Design. Prospective observational study. ...

OBJECTIVES: The WHO anatomical therapeutic chemical (ATC)/defined daily dose (DDD) methodology is a standardized method of comparing antimicrobial use. The ATC/DDD is defined as the average maintenance daily dose of a drug used in a 70 kg adult, ignoring the considerable differences in body weight of neonates and children. The ...

Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Cirak S, Arechavala-Gomeza V, Guglieri M, et al. (2011) The Lancet. 378 (9791): 595-605.

We report clinical safety and biochemical efficacy from a dose-ranging study of intravenously administered AVI-4658 phosphorodiamidate morpholino oligomer (PMO) in patients with Duchenne muscular dystrophy. We undertook an open-label, phase 2, dose-escalation study (0·5, 1·0, 2·0, 4·0, 10·0, and 20·0 mg/kg bodyweight) in ambulant patients with Duchenne muscular dystrophy aged ...

OBJECTIVE: To perform a double-blind, randomized study comparing efficacy and safety of daily and weekend prednisone in boys with Duchenne muscular dystrophy (DMD). METHODS: A total of 64 boys with DMD who were between 4 and 10 years of age were randomized at 1 of 12 centers of the Cooperative ...

Propofol anesthesia is often associated with decreased incidence of gagging, coughing or laryngospasm, and provides intense suppression on airway reflex during tracheal intubation and laryngeal mask airway insertion. Propofol pretreatment is also effective in reducing the occurrence of opioid-induced coughing. These benefits are often attributed to bronchodilator and sedative effects ...

Teicoplanin (TP) pharmacokinetics was assessed in a critically ill patient during albumin dialysis (AD), which was performed with the molecular adsorbent recirculating system. After a 1200-mg loading dose (24 mg/kg), doses of 1200 and 1000 mg (20 mg/kg) on day 2 and 3, respectively, were administered during two cycles of AD. The mean ...

Sedation during invasive procedures not only provides appropriate humanitarian care for patients, but also facilitates the completion of invasive procedures. Although generally safe and effective, adverse effects may occur especially in patients with co-morbid diseases. We present the successful use of a combination of dexmedetomidine and ketamine to provide sedation ...

Plexiform neurofibromas (PN) are a hallmark of neurofibromatosis type 1 (NF1). These large nerve tumors can be disfiguring and surgery is the only known standard therapy. Surgical intervention may be suboptimal due to the diffuse nature of PN. Here, we present a case in which we describe the use of ...

Manganese superoxide dismutase (MnSOD) is a genetically engineered therapeutic DNA/liposome containing the human MnSOD transgene. Preclinical studies in mouse models have demonstrated that the expression of the human MnSOD transgene confers protection of normal tissues from ionizing irradiation damage. This is a phase I study of MnSOD plasmid liposome (PL) ...

The deposition of amyloid-β (Aβ) peptides in plaques and intracellular neurofibrillary tangles are the two main characteristic pathological features of Alzheimer's disease (AD). Significantly, plaques are surrounded by activated astrocytes, microglia, and possibly, macrophages, and it has been suggested that this activity contributes to the pathology. Whether this will lead ...

Transcranial laser therapy (TLT) was tested for efficacy in a mouse model of Alzheimer's disease (AD) using a near-infrared energy laser system. TLT is thought to stimulate ATP production, increase mitochondrial activity, and help maintain neuronal function. Studies were performed to determine the effect of TLT in an amyloid-β protein ...

Elenine is the aglycone of elenoside, a cytotoxic arylnaphthalene lignan (NSC 644013-W/1) derived from Justicia hyssopifolia. (Family: Acanthaceae). Elenoside is a β-D-glucoside, with a similar chemical structure to etoposide, exhibiting central depressant activity. In the present study, elenine was given to mice and rats at doses of 10, 20, and ...

Weekly paclitaxel is an effective and widely used regimen for patients with advanced gastric cancer, with main dose-limiting toxicities of neutropenia and neurotoxicity. Neutropenia during weekly paclitaxel administration was reported to be associated with better survival. The aim of this study is to evaluate prospectively whether dosing adjustments based on ...

Prolonged fractionated oral administration of etoposide may present a theoretical advantage over intravenous administration of the bolus. This phase I trial was carried out to determine the recommended duration of oral etoposide in combination with a fixed dose of carboplatin. Nineteen patients with varied solid tumors, who were not candidates ...

Every-2-week (dose-dense) adjuvant doxorubicin (A) plus cyclophosphamide (C) followed by paclitaxel is a safe and effective adjuvant chemotherapy regimen. Every-3-week nab-paclitaxel is safe and more effective at 50% higher dose than every-3-week paclitaxel in metastatic breast cancer (BC). This study evaluated the safety of adjuvant dose-dense AC followed by dose-dense ...

Purpose This study intended to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RD) of trabectedin combined with carboplatin in patients with advanced solid tumors. Patients and methods Carboplatin-pretreated patients received carboplatin AUC 4 (Group 1), whereas carboplatin-naïve patients received carboplatin AUC 5 (Group 2) as ...

The aim of the present study was to investigate the effect of poly(acrylic acid)-cysteine (PAA-cysteine) exhibiting a molecular mass of 100 and 250 kDa and reduced glutathione (GSH) on the absorption of the P-glycoprotein (P-gp) and cytochrome P450 (CYP450) substrate paclitaxel in vitro and in vivo. In vitro transport studies ...

Chemotherapeutic drug dosages are calculated precisely based on the patient's height, body weight, and renal function, etc. To ensure safe and favorable outcomes of treatment, dosing solutions are prepared by appropriate mixing of the drug solutions based on such calculations. The package inserts for many injectable preparations include a warning ...

This Phase Ib dose-escalating study investigated safety, maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and clinical antitumour activity of tosedostat (CHR-2797), an orally bioavailable aminopeptidase inhibitor, in combination with paclitaxel. A total of 22 patients received paclitaxel (135-175 mg m(-2)) intravenously, administered once every three weeks for up to ...

Etoposide is used in a wide variety of solid and hematological tumors. It is available in Australia in two intravenous formulations; etoposide base and the etoposide phosphate salt with 113.6 mg of etoposide phosphate being equivalent to 100 mg of the etoposide base. Variances between the etoposide dose prescribed and ...

This trial aimed to define a recommended safe dose (RSD) of weekly paclitaxel and irinotecan combined with carboplatin in patients with advanced cancer. Patients with advanced cancer were eligible for this trial. Dose-limiting toxicity (DLT) was considered to be any grade greater than or equal to 3 (G> or =3) ...

The physicochemical characteristics, in vitro properties, and in vivo toxicity and efficacy of a third generation triazine dendrimer bearing approximately nine 2 kDa polyethylene glycol chains and twelve ester linked paclitaxel groups are reported. The hydrodynamic diameter of the neutral construct varies slightly with aqueous solvent ranging from 15.6 to ...

The aim of this study was to evaluate the pharmacokinetics of paclitaxel-loaded nanosponges (PLN) in rats. The study also evaluates the intrinsic effect of the dosage form on the improvement of paclitaxel oral bioavailability. Paclitaxel-loaded nanosponges were prepared and characterized in terms of size distribution, drug solubilization, and the kinetics ...

PURPOSE: Paclitaxel is an antiproliferative agent in drug-eluting stents with largely unknown tissue interaction. Toxicity might result from overdosage and/or accumulation. Part 1 of this two-step study investigated how paclitaxel uptake depends on dose density, coronary drug transfer kinetics, and elution efficacy. MATERIALS AND METHODS: With cobalt chromium stents and ...

Edotecarin (J-107088), a novel inhibitor of topoisomerase I has an additive effect on colon cell lines (HCT-116) when combined with 5-fluorouracil (5-FU). We conducted a phase I study to determine the maximum tolerated dose and recommended a phase II dose of edotecarin in combination with infusional 5-FU/leucovorin (LV) in patients ...

The prognosis of peritoneal carcinomatosis is regarded as poor because safe, effective therapeutic modalities are lacking. Intraperitoneal chemotherapy is one treatment option, involving the delivery of a high concentration of chemotherapeutic drugs into the abdominal cavity, but the severe side effects associated with such treatment are a major obstacle in ...

Oral mucositis (OM) is a frequent side effect in patients with cancer. We investigate the effect of atorvastatin (ATV), a cholesterol-lowering drug, on OM induced by 5-fluorouracil (5-FU) in hamsters. OM was induced by the i.p. administration of 5-FU, with excoriations of the cheek pouch mucosa. The animals were pretreated ...

Carboplatin is the most effective drug in retinoblastoma but systemic clearance is variable in young patients. While most regimens use a flat dose, individualized targeting may provide a more adjusted systemic exposure. We compared carboplatin doses between two groups of children with retinoblastoma that were treated using a flat dose ...

OBJECTIVE: This pilot open-label clinical study evaluated the safety and pharmacokinetics of albumin-bound paclitaxel (nab-paclitaxel) in patients with advanced solid tumors and hepatic dysfunction. RESEARCH DESIGN/METHODS: Dosing was determined according to baseline bilirubin levels as described in the package insert for Taxol((R)) (paclitaxel), and patients received 130, 200 or 260 ...

BACKGROUND: Although hepatic arterial infusion chemotherapy (HAIC) using low-dose 5-fluorouracil (5-FU) and cisplatin (low-dose FP) is commonly used for advanced hepatocellular carcinoma (HCC) with vascular invasion in Japan, few reports have investigated the efficacy and safety of this approach. We investigated the efficacy and toxicity of HAIC using low-dose FP ...

PURPOSE: To examine the safety of carboplatin-based chemotherapy and the applicability of the Calvert formula in patients with cancer who are undergoing hemodialysis. METHODS: We treated two patients who were undergoing hemodialysis and received carboplatin-based chemotherapy to treat non-small-cell lung cancer or ovarian cancer. The dose of carboplatin was calculated ...

This phase I study assessed the maximum tolerated dose, dose-limiting toxicity (DLT) and pharmacokinetics of belinostat with carboplatin and paclitaxel and the anti-tumour activity of the combination in solid tumours. Cohorts of three to six patients were treated with escalating doses of belinostat administered intravenously once daily, days 1-5 q21 ...

PURPOSE: This Phase I study was designed to determine a safe combination dose of 5-fluorouracil (5-FU) and arsenic trioxide (ATO) to treat 5-FU-resistant relapsed/refractory colorectal cancer patients. We studied the effect of ATO in the downregulation of thymidylate synthase (TS) in peripheral blood mononuclear cells and in tumor biopsies. EXPERIMENTAL ...

A randomized clinical trial examined whether dexamethasone administration prior to ondansetron followed by etoposide and carboplatin infusions, and single-nucleotide polymorphisms (SNPs) of CYP3A4, CYP3A5 and MDR1 genes could modify etoposide pharmacokinetics in pediatric patients. Patients, 67 children, aged 14 weeks to 16.7 years, were treated for various malignancies and received either 3- ...

PURPOSE: Dose-dense doxorubicin and cyclophosphamide (AC) followed by paclitaxel and trastuzumab (PT) is feasible. Lapatinib is effective in the treatment of human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer. We conducted a pilot study of dose-dense AC followed by PT plus lapatinib (PTL) followed by trastuzumab plus ...

We conducted a phase I clinical trial to determine the maximum tolerated dose (MTD) of daily or twice daily vorinostat x 3 days when combined with fixed doses of 5-fluorouracil (FU) and leucovorin every 2 weeks. Vorinostat doses were escalated in a standard 3 x 3 phase I design. FU/leucovorin ...

Paclitaxel (PTX) is approved for the treatment of ovarian and breast cancer. The commercially available preparation of PTX, Cremophor EL(R) is associated with hypersensitivity reactions in spite of a suitable premedication. In general, the developed liposomal PTX formulations are troubled with low PTX encapsulation capacity (maximal content, 3 mol%) and ...

The purpose of this study was to determine the life cycle and effectiveness of insecticides against bed bugs in Thailand. Bed bugs from dwelling places in Chon Buri and Chiang Mai provinces were determined to be Cimex hemipterus and Cimex lectularius, respectively. Both bed bug species were reared by feeding ...

Paclitaxel is a substrate of the efflux transporters such as P-glycoprotein, and is mainly metabolized by the liver. Schisandrol B (Sch B), one of the active components in Schisandra, has been reported to be able to inhibit the activity of P-gp and CYP3A. It might be possible that Sch B ...

PURPOSE: This phase I study evaluated the feasibility, safety, pharmacokinetics (PK), and preliminary evidence of anticancer activity of the sequential administration of paclitaxel and trabectedin on an every-2-week schedule in patients with refractory solid malignancies. The study also sought to determine the maximum tolerated dose (MTD) level on this schedule, ...

PURPOSE: Lipid nanocapsules (LNCs) are solvent-free drug nanocarriers permitting entrapment of paclitaxel and increasing its antitumoural effect in animal models after i.v. injection. The tolerance and efficacy of LNCs after repeated dose i.v. administration were assessed in mice. The maximum tolerated dose (MTD) and 50 percent lethal dose (LD50) were ...

PURPOSE: To determine the maximum tolerated dose of oblimersen, an antisense oligonucleotide directed to the Bcl-2 mRNA, in combination with cisplatin and 5-flourouracil in patients with advanced gastric and esophageal carcinoma. METHODS: Patients were treated with escalating doses of oblimersen administered by continuous intravenous infusion (CIVI) days 1 to 7, ...

The aim of this study was to determine the antimetastatic efficacy of the combination of 5-fluorouracil (5-FU), leucovorin (LV), and irinotecan (CPT-11) (FOLFIRI) in an orthotopic nude mouse model of GFP-HCT-116 human colon cancer-expressing green fluorescent protein (GFP). The mice were randomly divided into four groups: Group 1: saline control; ...

PURPOSE: Lenalidomide, a highly potent immunomodulatory derivative of thalidomide, potentiates the action of paclitaxel in vitro against prostate cancer cell lines in co-culture with mononuclear cells. A modular Phase I study of lenalidomide and paclitaxel in men with metastatic castration-resistant prostate cancer (CRPC) was conducted to assess PSA kinetics with ...

The purpose of this study was to develop a novel, highly water-soluble poly(L-γ-glutamyl-glutamine)-paclitaxel nanoconjugate (PGG-PTX) that would improve the therapeutic index of paclitaxel (PTX). PGG-PTX is a modification of poly(L-glutamic acid)- paclitaxel conjugate (PGA-PTX) in which an additional glutamic acid has been added to each glutamic side chain in the ...

BACKGROUND: Eniluracil is a potent inactivator of dihydropyrimidine dehydrogenase (uracil reductase), the enzyme that rapidly catabolizes 5-fluorouracil (5-FU). Although eniluracil in combination with 5-FU was promising in phase I and II studies, in 2 multicenter phase III colorectal cancer studies, eniluracil dosed in a 10-to-1 ratio to 5-FU produced less ...

Silibinin, a flavonoid, is an inhibitor of P-glycoprotein (P-gp)-mediated efflux transporters, and its oxidative metabolism is catalyzed by CYP3A4. The purpose of this study was to investigate the effect of oral silibinin on the bioavailability and pharmacokinetics of orally and intravenously administered paclitaxel in rats. The pharmacokinetic parameters of paclitaxel ...

OBJECTIVE: The effects of dose-escalation of 5-fluorouracil (5-FU) on the clinical outcome and pharmacokinetics of 5-FU were investigated in Japanese patients with Stage III/IVa esophageal squamous cell carcinoma. METHODS: Thirty-five patients with Stage III/IVa were enrolled, who were treated with a definitive 5-FU/cisplatin-based chemoradiotherapy. A course consisted of continuous infusion ...