Clinical therapeutics
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Clinical therapeutics · Sep 2007
Randomized Controlled TrialOromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial.
Central neuropathic pain (CNP), pain initiated or caused by a primary lesion or dysfunction of the central nervous system, occurs in ~28% of patients with multiple sclerosis (MS). Delta(9)-Tetrahydrocannabinol/cannabidiol (THC/CBD), an endocannabinoid system modulator, has demonstrated efficacy for up to 4 weeks in randomized controlled trials in the treatment of CNP in patients with MS. ⋯ THC/CBD was effective, with no evidence of tolerance, in these select patients with CNP and MS who completed approximately 2 years of treatment (n = 28). Ninety-two percent of patients experienced an AE, the most common of which were dizziness and nausea. The majority of AEs were deemed to be of mild to moderate severity by the investigators.
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Clinical therapeutics · Sep 2007
Comparative StudyEffects of liposomal amphotericin B versus an amphotericin B lipid complex on liver histopathology in patients with hematologic malignancies and invasive fungal infections: a retrospective, nonrandomized autopsy study.
Abnormal liver function test (LFT) results are common in patients with hematologic abnormalities, making the assessment of drug-related hepatotoxicity difficult. Studies based on elevated LFT levels have found that use of liposomal amphotericin B (L-AMB) was associated with increased hepatotoxicity compared with amphotericin B (AMB)/deoxycholate or amphotericin B lipid complex (ABLC). Because LFT abnormalities are multifactorial in severely immunocompromised patients, uncertainty remains regarding the clinical significance of these laboratory findings. ⋯ Although abnormal results on LFT and/or histopathologic changes in liver were found in 92% of these debilitated patients with hematologic malignancy, direct histopathologic evidence of toxicity associated with lipid formulations of AMB was not established in our study.
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Clinical therapeutics · Sep 2007
Comparative StudyDosing intervals and hemoglobin control in patients with chronic kidney disease and anemia treated with epoetin alfa or darbepoetin alfa: a retrospective cohort study.
Anemia is a common complication of chronic kidney disease (CKD). The approved dosing interval for currently available erythropoiesis-stimulating agents (ESAs) is 2 to 3 times weekly for epoetin alfa (EPO) and every 1 to 2 weeks for darbepoetin alfa (DARB). However, clinicians sometimes use less frequent dosing in the interest of convenience. ⋯ The patterns of ESA usage in adult outpatients with CKD at this center indicated that clinicians extended dosing intervals beyond those in the approved prescribing information. However, variations in Hb concentrations occurred during maintenance therapy administered at extended dosing intervals, resulting in the resumption of shorter dosing intervals in the majority of patients.
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Clinical therapeutics · Aug 2007
ReviewReducing the risk for breast cancer recurrence after completion of tamoxifen treatment in postmenopausal women.
In postmenopausal women with hormone-sensitive early stage breast cancer, the risk for relapse persists after 5 years of treatment with adjuvant tamoxifen. Because tamoxifen is not indicated for adjuvant therapy beyond 5 years, the need for another therapy in the extended adjuvant setting to reduce late recurrence risk is clear. The National Cancer Institute of Canada Clinical Trials Group MA.17 and the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-33 trial found that extended adjuvant therapy with an aromatase inhibitor (AI) (eg, letrozole, exemestane, or anastrozole) rendered additional benefit in postmenopausal women with hormone receptor-positive breast cancer. The MA.17 trial was unblinded at the first interim analysis (median follow-up, 2.4 years) due to a significant reduction in relative risk for recurrence (P < 0.001). Following the publication of the final analysis, several other MA.17 trial analyses and a postblinding analysis were also conducted. Recent data on the NSABP B-33 trial, which investigated exemestane in the extended adjuvant setting, and Austrian Breast and Colorectal Cancer Study Group (ABCSG) trial 6a, which evaluated anastrozole in the extended adjuvant setting, have also been reported. ⋯ Current evidence supports the use of letrozole and perhaps exemestane in the extended adjuvant setting, while data on anastrozole are emerging. Based on the results from this review, initiation of letrozole treatment following a prolonged interval after completion of 5 years of tamoxifen treatment might be beneficial.
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Clinical therapeutics · Aug 2007
Randomized Controlled TrialPharmacokinetic and pharmacodynamic assessments of the dipeptidyl peptidase-4 inhibitor PHX1149: double-blind, placebo-controlled, single- and multiple-dose studies in healthy subjects.
PHX1149 is a dipeptidyl peptidase-4 (DPP4) inhibitor that is currently in clinical development for the treatment of type 2 diabetes mellitus. PHX1149 is a small (molecular weight = 241.16 Da), highly water-soluble (>2 g/mL), orally active molecule with a selectivity index of 15- to 319-fold relative to those of other members of the DPP family. The biochemical median inhibitory concentration of DPP4 is 2.5 nmol/L. ⋯ The PK parameters and PD properties of PHX1149 were suitable (eg, tl/2, DPP4 inhibition) for once-daily dosing in this group of 58 healthy subjects. All doses were well tolerated.