Pharmacokinetic modeling of the blood-stable camptothecin analog AR-67 in two different formulations.

AR-67 is a lipophilic camptothecin analog currently under clinical investigation using a Cremophor EL based formulation. However, as potential toxicity limitations exist in the clinical use of Cremophor, an alternative cyclodextrin (SBE-β-CD) based formulation has been proposed. Pharmacokinetic (PK) studies were conducted in mice and the SBE-β-CD based formulation was compared with the Cremophor EL formulation.

Effect of modifying dose alerts in an electronic health record on frequency of alerts.

Purpose: Results of a study to reduce the number of medication order-entry alerts and perceived alert fatigue by optimizing alert logic are reported.

Methods: Data on dosage alerts registered throughout a health system over 2 days per study phase (preintervention and postintervention) were collected from the electronic health record. The 5 medications most frequently associated with dosage alerts during computerized prescriber order entry (CPOE) were evaluated for appropriateness in relation to patient-specific characteristics.

Vancomycin Pharmacokinetics Throughout Life: Results from a Pooled Population Analysis and Evaluation of Current Dosing Recommendations.

Background And Objectives: Uncertainty exists regarding the optimal dosing regimen for vancomycin in different patient populations, leading to a plethora of subgroup-specific pharmacokinetic models and derived dosing regimens. We aimed to investigate whether a single model for vancomycin could be developed based on a broad dataset covering the extremes of patient characteristics. Furthermore, as a benchmark for current dosing recommendations, we evaluated and optimised the expected vancomycin exposure throughout life and for specific patient subgroups.

Evaluation of a Pharmacist-Managed Heart Failure Education Project: Empowering Patients to Self-Manage Their Disease.

Recent reimbursement cuts for hospitals with higher 30-day heart failure (HF)-related readmission rates call for means of reducing those readmissions. To determine if pharmacist-initiated education increases HF knowledge and assess if an increase in HF knowledge decreases HF readmission. This was a prospective interventional study.

Single-dose dexamethasone for the prevention of pemetrexed associated cutaneous adverse reactions.

Pemetrexed (Alimta®) is a novel anti-folate antimetabolite agent that is used in combination with cisplatin for the treatment of patients with unresectable malignant pleural mesothelioma and as a single agent or in combination with cisplatin for patients with locally advanced or metastatic non-small-cell-lung-cancer. Cutaneous adverse reactions are common side effects of pemetrexed for which the manufacturer recommends 3-day premedication with dexamethasone 4 mg by mouth twice daily-(the day before, the day of, and the day after treatment). Patients' adherence to this premedication regimen is of concern.

Pharmacokinetics of vancomycin in extremely obese patients with suspected or confirmed Staphylococcus aureus infections.

Study Objective: To estimate vancomycin pharmacokinetic parameters and dosing requirements in a cohort of extremely obese patients.

Design: Prospective pharmacokinetic study.

Setting: Acute care community teaching hospital.

Protracted dosing of the lipophilic camptothecin analogue AR-67 in non-small cell lung cancer xenografts and humans.

Purpose: Although preclinical studies on camptothecin antitumor effect have demonstrated the superiority of low-dose protracted dosing, these findings were not replicated in the clinic. 7-t-butyldimethylsilyl-10-hydroxycamptothecin (AR-67) is a camptothecin analogue currently under investigation in early phase clinical trials. To maximize the therapeutic potential of AR-67, we sought to identify factors that affect response to treatment.

The effect of breast cancer resistance protein, multidrug resistant protein 1, and organic anion-transporting polypeptide 1B3 on the antitumor efficacy of the lipophilic camptothecin 7-t-butyldimethylsilyl-10-hydroxycamptothecin (AR-67) in vitro.

AR-67 (7-t-butyldimethylsilyl-10-hydroxycamptothecin) is a lipophilic camptothecin analog, currently under early stage clinical trials. Transporters are known to have an impact on the disposition of camptothecins and on the response to chemotherapeutics in general due to their expression in tumor tissues. Therefore, we investigated the interplay between the breast cancer resistance protein (BCRP), multidrug resistant protein 1 (MDR1), and organic anion-transporting polypeptide (OATP) 1B1/1B3 transporters and AR-67 and their impact on the toxicity profile of AR-67.

Pharmacokinetic modeling to assess factors affecting the oral bioavailability of the lactone and carboxylate forms of the lipophilic camptothecin analogue AR-67 in rats.

Purpose: Camptothecin analogues are anticancer drugs effective when dosed in protracted schedules. Such treatment is best suited for oral formulations. AR-67 is a novel lipophilic analogue with potent efficacy in preclinical models.

Factors affecting the in vivo lactone stability and systemic clearance of the lipophilic camptothecin analogue AR-67.

Purpose: The narrow efficacy-toxicity window of anticancer agents necessitates understanding of factors contributing to their disposition. This is especially true for camptothecins as they exist in the lactone and carboxylate forms with each moiety differentially interacting with efflux or uptake transporters. Here we determined the disposition of the lactone and carboxylate forms of AR-67, a 3(rd) generation camptothecin analogue.