Two animal studies were conducted to determine the feasibility of infusing treprostinil via a central venous catheter at an infusion rate of 0.1 mL/hour. Currently treprostinil is administered intravenously at infusion rates of approximately 1.0 to 2.0 mL/hour to patients with pulmonary arterial hypertension, which reflects standard clinical practice to ensure line patency with continuous intravenous administration via a central venous catheter.

Methods:

In a pilot study three male beagle dogs were administered 50 ng/kg/min of treprostinil continuously at an infusion rate of 0.1 mL/hr via the MiniMed 407C infusion pump for 21 days. In a definitive study, six male beagle dogs were administered 50 ng/kg/min of treprostinil continuously at an infusion rate of 0.1 mL/hr via the MiniMed 407C infusion pump for 60 days. In both studies “no delivery” pump alarms were documented throughout the study in addition to pharmacokinetic data at specified time points.

Results:

There were no documented occlusions in the 21-day pilot study. In the 60-day study one animal had a documented catheter occlusion after 16 days of therapy. Following re-implantation with a new catheter this animal did not have any additional occlusions for 40 days. No other animals in this study had any significant problems. In both studies, pharmacokinetic data were similar to that observed in previous animal studies evaluating treprostinil administration at the same dose and at higher infusion rates.

Conclusion:

These animal data support the evaluation of administering treprostinil at a low infusion rate via the MiniMed 407C infusion pump in patients with pulmonary arterial hypertension.

2003-12-31·JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES

Improvement of Sensitivity for the Determination of Propylene Glycol in Rat Plasma and Lung Tissue Using HPLC/Tandem MS and Derivatization with Benzoyl Chloride

作者: McGuire, Gerard M. ; Thomas Karnes, H. ; Wilson, David M. ; Edinboro, Leslie E. ; Gao, Songmei ; Williams, Stephen G. P.

Propylene glycol (PG), a simple alc., is a commonly used vehicle for aerosol dosage formulations.Quantification of PG in plasma and lung tissue is, therefore, important for new drug development.The authors describe a highly sensitive and selective method for the quant. determination of PG in rat plasma and lung tissue, using liquid chromatog. (LC) with pos. atm. pressure chem. ionization (APCI) tandem mass spectrometry (MS) detection.Propylene glycol and the internal standard (IS) 1,4-butanediol were derivatized with benzoyl chloride under alk. conditions to enhance the sensitivity of detection.Ionization efficiency was improved following derivatization.The limits of detection (LOD) for rat plasma and rat lung tissue were 0.269 μg/mL and 1.12 μg/g, resp.The LOQs for rat plasma and lung tissue were 0.448 μg/mL and 1.62 μg/g, resp.Calibration curves were linear from 2 to 4000 μg/mL for rat plasma (r = 0.9990) and from 2 to 2400 μg/g for rat lung tissue (r = 0.9985).The assay showed intra-assay and inter-assay precision (%RSD) of 3.8-4.8% (n = 6) and 4.2-6.6% (n = 18) for rat plasma, 3.8-4.0% (n = 6) and 6.5-7.4% (n = 18) for rat lung tissue, resp.The percent inaccuracy for inter-assay results in rat plasma were 2.5-4.7% and in rat lung tissue were 1.3-6.8% for different concentrationsAll plasma and lung tissue samples demonstrated acceptable freeze/thaw stability, bench stability, and prepared sample stability over a 24 h period.An alternative derivatizing method using perfluorooctanoyl chloride with neg. APCI/MS detection was investigated.Although strong fragment ions of the derivatives could be detected, the feasibility of this method was limited by sample preparationAddnl., fragment ions produced from the perfluorooctanoyl moiety lacked selectivity.The benzoyl chloride method is proved to be more sensitive, selective, and robust.

2003-10-01·Anesthesiology1区 · 医学

Pharmacokinetics of an Implanted Osmotic Pump Delivering Sufentanil for the Treatment of Chronic Pain

1区 · 医学

Article

作者: Kellett, Norma ; Lenhardt, Rainer ; Fisher, Dennis M.

Background:

A matchstick-sized implanted osmotic pump (Chronogesic) that delivers sufentanil subcutaneously for more than 90 days is being developed to treat chronic pain. This study evaluates pharmacokinetic characteristics related to the absorption of sufentanil using a prototype 60-day system.

Methods:

Twelve opioid-naive volunteers were given naltrexone to prevent opioid effects. Sufentanil, 60 microg, was infused intravenously over 6 h, then 48 h later, the pump was implanted subcutaneously in the upper arm under local anesthesia. Pumps were removed 9 days later. In six volunteers, fever (1.6-3.3 degrees C) was induced with interleukin-2. Plasma was sampled and population pharmacokinetic modeling was performed to estimate in vivo release rate and absorption half-life. Bioavailability was calculated by comparing in vivo to in vitro release rates. The impact of perturbations in release rate on sufentanil plasma concentration (Cp) was simulated.

Results:

Fever had no systematic effect on Cp. Release rate estimated in vivo was similar to that measured in vitro; bioavailability did not differ from 100%. Absorption half-life was 16.2 h. Simulation demonstrated that supplemental release of sufentanil from the implant (as might occur with local heating) increases Cp an average of 2.5-2.8% per hours supplemental dose.

Conclusions:

An implantable osmotic pump delivered sufentanil in vivo at the rate predicted from in vitro experiments. The rate at which sufentanil was absorbed from the subcutaneous space (half-life > 16 h) was markedly slower than reported with subcutaneous or intramuscular administration of large volumes of dilute opioids; this slow absorption dampens potential changes in Cp if release rate is perturbed.

项与 Inveresk Research Group, Inc. 相关的新闻（医药）

2023-04-05

·Business Wire

Kindeva Drug Delivery Announces the Appointment of David Stevens as Global CCO

ST. PAUL, Minn. & ST. LOUIS--( BUSINESS WIRE )-- Kindeva Drug Delivery (Kindeva), a leading global contract development and manufacturing organization (CDMO) focused on drug-device combination products, announced that David Stevens has joined the organization as global chief commercial officer (CCO). Stevens will spearhead the commercial, business development, and research and development activities for the business to ensure continued growth, expansion, and innovation. “David brings a breadth of industry experience and a depth of commercial expertise that is essential for driving Kindeva’s enhanced scope and scale,” said Kindeva CEO Milton Boyer . “His role is vital to our continued success as a premier CDMO and, in turn, the success of our partners bringing a broad range of drug delivery solutions to market.” Stevens has more than 20 years of international operations and commercial experience across both the CDMO and contract research organization (CRO) sectors. Prior to Kindeva, Stevens was CEO of advanced therapy CDMO Arranta Bio (acquired by Recipharm in 2022), where he successfully built out two advanced biologics development and GMP manufacturing facilities. He held multiple roles at AMRI prior — leading the company’s drug product business unit through significant growth and capacity expansion. Throughout his tenure, he also held positions at Aptuit, Inveresk, and Charles River Laboratories. Stevens has an MBA in strategy, finance, and marketing from the University of Edinburgh. “The Kindeva organization has a strong history of achievement, expertise, and the infrastructure to handle an extensive range of critical complex drug delivery challenges,” Stevens said. “I am excited to work with the incredible experts bringing many life-changing therapies and the highest-quality products to patients, and I am looking forward to leveraging my commercial, operational, and strategic background to enable continued success for our partners worldwide.” About Kindeva Drug Delivery Kindeva is a global contract development manufacturing organization focused on drug-device combination products. Kindeva develops and manufactures products across a broad range of complex drug-delivery formats, including autoinjectors, inhalers, transdermal patches, and microneedles. Its service offering spans early-stage feasibility through commercial scale drug product fill-finish, container closure system manufacturing and drug-device product assembly. Kindeva serves a global client base from its nine manufacturing and research and development facilities located in the U.S. and U.K. For more information, please visit www.kindevadd.com .

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