Details about the type of analysis (e.g., intent to treat [ITT]) and definitions (i.e., criteria for including participants in the analysis) are necessary for interpreting a clinical trial’s findings. Our objective was to compare the description of types of analyses and criteria for including participants in the publication (i.e., what was reported) with descriptions in the corresponding internal company documents (i.e., what was planned and what was done). Trials were for off-label uses of gabapentin sponsored by Pfizer and Parke-Davis, and documents were obtained through litigation.
The pharmacokinetics of maropitant citrate dosed orally to dogs at 2 mg/kg and 8 mg/kg once daily for 14 days consecutive days.
- Journal of veterinary pharmacology and therapeutics
- Published over 7 years ago
The pharmacokinetics of maropitant were evaluated in beagle dogs dosed orally with Cerenia(®) tablets (Pfizer Animal Health) once daily for 14 consecutive days at either 2 mg/kg or 8 mg/kg bodyweight. Noncompartmental pharmacokinetic analysis was performed on the plasma concentration data to measure the AUC(0-24) (after first and last doses), C(t) (trough concentration-measured 24 h after each dose), C(max) (after first and last doses), t(max) (after first and last doses), λ(z) (terminal disposition rate constant; after last dose), t(½) (after last dose), and CL/F (oral clearance; after last dose). Maropitant accumulation in plasma was substantially greater after fourteen daily 8 mg/kg doses than after fourteen daily 2 mg/kg doses as reflected in the AUC(0-24) accumulation ratio of 4.81 at 8 mg/kg and 2.46 at 2 mg/kg. This is most likely due to previously identified nonlinear pharmacokinetics of maropitant in which high doses (8 mg/kg) saturate the metabolic clearance mechanisms and delay drug elimination. To determine the time to reach steady-state maropitant plasma levels, a nonlinear model was fit to the least squares (LS) means maropitant C(t) values for each treatment group. Based on this model, 90% of steady-state was determined to occur at approximately four doses for daily 2 mg/kg oral dosing and eight doses for daily 8 mg/kg oral dosing.
Evaluation of an extended-release formulation of ceftiofur crystalline-free acid in koi (Cyprinus carpio)
- Journal of veterinary pharmacology and therapeutics
- Published over 5 years ago
The use of an extended release ceftiofur crystalline-free acid formulation (CCFA, Excede For Swine(®) , Pfizer Animal Health) in koi was evaluated after administration of single intramuscular (i.m.) or intracoelomic (i.c.) doses. Twenty koi were divided randomly into a control group and four treatment groups (20 mg/kg i.m., 60 mg/kg i.m., 30 mg/kg i.c., and 60 mg/kg i.c.). Serum ceftiofur-free acid equivalents (CFAE) concentrations were quantified. The pharmacokinetic data were analyzed using a nonlinear mixed-effects approach. Following a CCFA injection of 60 mg/kg i.m., time durations that serum CFAE concentrations were above the target concentration of 4 μg/mL ranged from 0.4 to 2.5 weeks in 3 of 4 fish, while serum CFAE concentrations remained below 4 μg/mL for lower doses evaluated. Substantial inter-individual variations and intra-individual fluctuations of CFAE concentrations were observed for all treatment groups. Histological findings following euthanasia included aseptic granulomatous reactions, but no systemic adverse effects were detected. Given the unpredictable time vs. CFAE concentration profiles for treated koi, the authors would not recommend this product for therapeutic use in koi at this time. Further research would be necessary to correlate serum and tissue concentrations and to better establish MIC data for Aeromonas spp. isolated from naturally infected koi.
To compare sildenafil plus hydration with hydration alone in improving the amniotic fluid index and neonatal outcomes in pregnancies complicated by idiopathic oligohydramnios ( amniotic fluid index less than 5 cm without underlying maternal or fetal causes and with normal fetal growth).
In this work, we describe a new approach for the characterization of process-related impurities along with an in silico tool to generate orthogonal, integrated downstream purification processes for biological products. A one-time characterization of process-related impurities from product expression in Pichia pastoris was first carried out using linear salt and pH gradients on a library of multimodal, salt-tolerant, and hydrophobic charge induction chromatographic resins. Reversed phase UPLC analysis of the fractions from these gradients was then used to generate large data sets of impurity profiles. A retention database of the biological product was also generated using the same linear salt and pH gradients on these resins, without fraction collection. The resulting two data sets were then analyzed using an in silico tool, which incorporated integrated manufacturing constraints to generate and rank potential 3-step purification sequences based on their predicted purification performance, as well as whole-process “orthogonality” for impurity removal. Highly ranked sequences were further examined to identify templates for process development. The efficacy of this approach was successfully demonstrated for the rapid development of robust integrated processes for human growth hormone (hGH) and granulocyte-colony stimulating factor (G-CSF). This article is protected by copyright. All rights reserved.
Cigarette smoking is the leading preventable cause of death and is responsible for more than 480,000 deaths per year in the United States. Smoking cessation is challenging for many patients. Regardless of available treatment options, most quit attempts are unaided, and it takes multiple attempts before a patient is successful. With the ever-increasing use of smartphones, mobile apps hold promise in supporting cessation efforts. This study evaluates the ease of use and user satisfaction with the Pfizer Meds app to support smoking cessation among patients prescribed varenicline (Chantix).
A robust, rapid and sensitive UPLC-MS/MS method has been developed, optimized and validated for determination of amlodipine (AML) and atorvastatin (ATO) in human plasma using eplerenone as an internal standard (IS). Multiple-reaction monitoring in positive electrospray ionization mode was utilized in Xevo TQD LC-MS/MS. Double extraction was used in sample preparation using diethyl ether and ethyl acetate. The prepared samples were analyzed using Acquity UPLC BEH C18(50 x 2.1 mm, 1.7 μm) column. Ammonium formate and acetonitrile, pumped isocraticaly at a flow rate of 0.25 ml/min., were used as a mobile phase. Method validation was done as per the FDA guidelines. Linearity was achieved in the range of 0.1-10 ng/ml for AML and 0.05-50 ng/ml for ATO. Intra-day and inter-day accuracy and precision were calculated and found to be within the acceptable range. A short run time, of less than 1.5 minutes, permits analysis of a large number of plasma samples per batch. The developed and validated method was applied to estimate AML and ATO in a bioequivalence study in healthy human volunteers.
We report a fatal case of Candida auris that was involved in mixed candidemia with Candida tropicalis, isolated from the blood of a neutropenic patient. Identification of both isolates was confirmed by amplification and sequencing of internal transcribed spacer and D1/D2 domain of large subunit in rRNA gene. Antifungal susceptibility test by E-test method revealed that C. auris was resistant to amphotericin B, anidulafungin, caspofungin, fluconazole, itraconazole and voriconazole. On the other hand, C. tropicalis was sensitive to all antifungal tested. The use of chromogenic agar as isolation media is vital in detecting mixed candidemia.
BACKGROUND Neuromyelitis optica (NMO) is a rare demyelinating disease of the central nervous system; NMO predominantly affects the spinal cord and optic nerves. The diagnosis is based on history, clinical presentation, seropositive NMO-IgG antibody, and notably, exclusion of other diseases. Despite the absence of definitive therapeutic strategies for NMO, methylprednisolone pulse therapy and plasma exchange are used for acute phase treatment, while immunosuppressive agent(s) are recommended to prevent relapses and improve prognosis. Here, we report a repeating relapse NMO case due to lack of regular and maintenance therapy. CASE REPORT A 58-year-old female with chronic NMO presented with a three-day history of new-onset right leg weakness and pain. The patient was diagnosed with NMO three years ago and presented with her fourth attacks. During her initial diagnosis, she was initiated on steroids. One year later, she developed the first relapse and was treated with steroids and rituximab, leading to 1.5-year remission. After the second relapse, steroids and rituximab was still given as maintenance therapy, but was not followed. Thus, the third relapse occurred in five months. During this hospitalization, she received initially high-dose solumedrol (1 g daily for five days) in addition to gabapentin 100 mg (gradually increased to 300 mg) three times a day for muscle spasms. Due to worsening of paresthesia and hemiparesis, it was decided to place her on plasma exchange treatment. After two plasma exchanges, the patient’s condition was improved and she regained strength in her lower extremity. She completed five more cycles of plasma exchange, and was then discharged on steroid therapy (prednisone 20 mg daily for 10 days then taper) as maintenance therapy and with follow-up in neurology clinic. CONCLUSIONS Over the span of three years, the patient has had three relapses since her NMO diagnosis where her symptoms have worsened. Steroid therapy alone seemed not insufficient in managing her more recent relapses. Nonadherence to NMO treatment likely increased her risk for recurrence, thus regular and long-term maintenance therapy is imperative to delay the progression and prevent relapse in NMO.
There is currently an absence of high-grade evidence regarding the treatment of chronic sciatica (CS). Whilst gabapentin (GBP) and pregabalin (PGB) are both currently used to treat CS, equipoise exists regarding their individual use. In particular, no head-to-head study of GBP and PGB in CS exists. Despite equipoise, most countries' formulary regulatory authorities typically favour one drug for subsidy over the other. This hinders interchange wherever the favoured drug is either ineffective or not tolerated. The primary aim of this study is to conduct a head-to-head comparison of the efficacy of PGB versus GBP for CS based on outcomes on a visual analogue scale (VAS) and the Oswestry Disability Index (ODI).