scholarly journals Pharmacokinetics of Injectable, Long-Acting Nevirapine for HIV Prophylaxis in Breastfeeding Infants

2014 ◽  
Vol 59 (1) ◽  
pp. 59-66 ◽  
Author(s):  
John M. Cortez ◽  
Rafaela Quintero ◽  
John A. Moss ◽  
Martin Beliveau ◽  
Thomas J. Smith ◽  
...  
Keyword(s):  
Sustained Release ◽  
Release Kinetics ◽  
Subcutaneous Administration ◽  
Rat Plasma ◽  
World Health ◽  
Pharmacokinetic Analysis ◽  
Successful Implementation ◽  
Time Data ◽  
Prophylactic Regimen ◽  
Long Acting

ABSTRACTMother-to-child transmission (MTCT) of HIV-1 remains a global health problem. The World Health Organization (WHO) recommendations advise the administration of a once-daily, oral, prophylactic regimen of the nonnucleoside reverse transcriptase inhibitor nevirapine (NVP) from birth until 4 to 6 weeks of age for infants born to HIV-infected mothers in regions without access to safe and nutritionally adequate alternatives to breast milk. A critical factor driving the successful implementation of the WHO guidelines involves sustaining high adherence to the frequent dosing. With these challenges in mind, we have developed the first injectable, sustained-release NVP formulations with the goal of providing, for 6 weeks or longer, preventative plasma drug levels from a single subcutaneous administration at birth. The long-acting NVP consists of large (>50 μm), monodisperse NVP particles coated with biocompatible polymers that control the drug release kinetics. Two lead formulations exhibiting burst-free, sustained-release kinetics for up to 75 daysin vitrowere developed. Subsequentin vivostudies in rats demonstrated no toxicity related to the formulations. Rat plasma NVP concentrations were above the analytical assay's limit of quantification for up to 28 days. Pharmacokinetic analysis of the rat plasma NVP concentration-time data allowed absorption rate constants to be calculated. These data then were used to simulate infant NVP exposure from a single injected dose (<200 mg) of our long-acting formulations, demonstrating preliminary feasibility of the technology to maintain safe, preventative NVP plasma levels (0.2 to 3.0 μg ml−1) for 6 weeks or longer.

scholarly journals Pharmacokinetics and Immunogenicity of Frunevetmab in Osteoarthritic Cats Following Intravenous and Subcutaneous Administration

2021 ◽  
Vol 8 ◽  
Author(s):  
Rodney R. Walters ◽  
Joseph F. Boucher ◽  
Flavia De Toni
Keyword(s):  
Drug Exposure ◽  
Subcutaneous Administration ◽  
Field Studies ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Time Data ◽  
Drug Levels ◽  
Trough Concentrations

Osteoarthritis and other degenerative joint diseases are common causes of chronic pain in cats. Frunevetmab is a felinized monoclonal antibody that binds to nerve growth factor (NGF) and provides relief from pain by blocking the receptor-mediated signaling cascade induced by NGF. Results from three studies were combined to provide an overview of frunevetmab pharmacokinetics (PK) and immunogenicity. The objective of the first study was to establish the pharmacokinetic parameters resulting from intravenous (IV) and subcutaneous (SC) administration of frunevetmab to the feline patient population at 3 mg/kg. Ten adult cats with naturally-occurring osteoarthritis were administered frunevetmab in a crossover design at 28 day intervals. Non-compartmental pharmacokinetic analysis of the plasma concentration-time data showed that the half-life was 10.1 ± 1.9 days after IV dosing and the SC bioavailability was 60.3 ± 15.8% with maximum drug levels observed at 3–7 days after dosing. Plasma samples were collected at ~28 days after dosing during two field safety and effectiveness studies of cats with degenerative joint disease. The doses ranged from 1.0 to 2.8 mg/kg; 2 or 3 doses were administered either SC/IV, SC/SC, or SC/SC/SC. The data from these studies along with the data from the laboratory pharmacokinetic study were analyzed using non-linear mixed-effects (NLME) modeling. The model closely predicted the trough concentrations from the two field studies, including the IV treatment in the pilot field study. The trough concentrations were predicted to be close to steady-state after 2 doses. A second objective was to determine the incidence and clinical relevance of frunevetmab immunogenicity. A three-tier anti-drug antibody assay (screen, confirm, titer) was developed and validated. Immunogenicity was assessed in 259 frunevetmab-treated animals enrolled in the two field studies. Only 4 of these animals (1.5%) appeared to develop immunogenicity to frunevetmab. None of the four exhibited adverse events attributed to immunogenicity and no impact on drug levels or efficacy was observed in three of the animals. In the placebo animals, 2.3% (3/131) appeared to develop treatment-emergent immunogenicity. Overall, frunevetmab administration resulted in a very low incidence of treatment-emergent immunogenicity with no safety findings and minimal effect on drug exposure and efficacy.

scholarly journals Formulation, Development and Evaluation of Gastroretentive Sustained Release Tablets of Lansoprazole Using Natural Polymer

2021 ◽  
Vol 11 (5-S) ◽  
pp. 108-112
Author(s):  
, Sonam ◽  
Nilesh Jain ◽  
Jitendra Banveer
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Acid Secretion ◽  
Release Kinetics ◽  
Natural Polymers ◽  
Formulation Development ◽  
Sustained Drug Release ◽  
Multiple Dosing ◽  
Long Acting

The goal of this study is to develop a long-acting Lansoprazole delivery system. Lansoprazole belongs to a class of antisecretory drugs known as substituted benzimidazoles, which decrease gastric acid secretion by inhibiting the (H+,K+)-ATPase enzyme system at the secretory membrane of the stomach parietal cell. Due to its mechanism of action, despite its short half-life of 1-5 hours, it can effectively block acid secretion for 24 hours. However, as his plasma concentration falls, the effect will diminish. Lansoprazole will be given as a sustained release tablet to avoid multiple dosing or to reduce the frequency of dose. Lansoprazole was produced and analysed utilizing natural and synthetic polymers such as Xanthan gum, Gellan gum, Carbopol 940 P, and Chitosan. Based on the findings of this experiment, it was determined that formulation F7 demonstrated sustained drug release for up to 12 hours in all developed formulations. Formulation (F1, F2, F3, F4, F5, and F6) were tested in vitro for drug release. For the improved formulation F7, the formulation and release kinetics were estimated. When the regression coefficient values of were evaluated, it was found that Peppas had the highest ‘r2' value, 0.952, indicating that drug release from formulations followed Peppas release kinetics. Key words: Lansoprazole, Sustain release tablets, Synthetic and Natural Polymers, formulation, evaluation

scholarly journals Lessons learned from implementation of the Workload Indicator of Staffing Need (WISN) methodology: An international Delphi study of expert users.

2021 ◽  
Author(s):  
Grace Nyendwoha Namaganda ◽  
Audrey Whitright ◽  
Everd Bikaitwoha Maniple
Keyword(s):  
Delphi Study ◽  
Scale Up ◽  
Lessons Learned ◽  
World Health ◽  
Small Scale ◽  
Successful Implementation ◽  
Time Data ◽  
Implementation Challenges ◽  
Health Organization ◽  
First Time

Abstract BackgroundStaffing of health services ought to consider the workload experienced to maximize efficiency. However, this is rarely the case, due to lack of an appropriate approach. The World Health Organization (WHO) developed and has promoted the Workload Indicators of Staffing Need (WISN) methodology globally. Due to its relative simplicity compared to previous methods, the WISN has been used extensively, particularly after its computerization in 2010. Many lessons have been learnt from the introduction and promotion of the methodology across the globe but have, hitherto, not been synthesized for technical and policy consideration. This study gathered, synthesized, and now shares the key adaptations, innovations, and lessons learned. These could facilitate lesson-learning and motivate the WHO’s WISN Thematic Working Group to review and further ease its application.MethodsThe study aimed to answer four questions: (1) how easy is it for the users to implement each step of the WISN methodology? (2) what innovations have been used to overcome implementation challenges? (3) what lessons have been learned that could inform future WISN implementation? and (4) what recommendations can be made to improve the WISN methodology? We used a three-round traditional Delphi method to conduct a case study of user-experiences during the adoption of the WISN methodology. We sent three email iterations to 23 purposively selected WISN expert users across 21 countries in five continents. Thematic analysis of each round was done simultaneously with data collection.ResultsParticipants rated seven of the eight technical steps of the WISN as either “very easy” or “easy” to implement. The step considered most difficult was obtaining the Category Allowance Factors (CAF). Key lessons learned were that: the benefits gained from applying the WISN outweigh the challenges faced in understanding the technical steps; benchmarking during WISN implementation saves time; data quality is critical for successful implementation; and starting with small-scale projects sets the ground better for more effective scale-up than attempting massive national application of the methodology the first time round. ConclusionsThe study provides a good reference for easing WISN implementation for new users and for WHO to continue promoting and improving upon it.

scholarly journals Development of In Situ Self-Assembly Nanoparticles to Encapsulate Lopinavir and Ritonavir for Long-Acting Subcutaneous Injection

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 904
Author(s):  
Irin Tanaudommongkon ◽  
Asama Tanaudommongkon ◽  
Xiaowei Dong
Keyword(s):  
Sustained Release ◽  
Trough Concentration ◽  
Self Assembly ◽  
Subcutaneous Injection ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Long Acting

Most antiretroviral medications for human immunodeficiency virus treatment and prevention require high levels of patient adherence, such that medications need to be administered daily without missing doses. Here, a long-acting subcutaneous injection of lopinavir (LPV) in combination with ritonavir (RTV) using in situ self-assembly nanoparticles (ISNPs) was developed to potentially overcome adherence barriers. The ISNP approach can improve the pharmacokinetic profiles of the drugs. The ISNPs were characterized in terms of particle size, drug entrapment efficiency, drug loading, in vitro release study, and in vivo pharmacokinetic study. LPV/RTV ISNPs were 167.8 nm in size, with a polydispersity index of less than 0.35. The entrapment efficiency was over 98% for both LPV and RTV, with drug loadings of 25% LPV and 6.3% RTV. A slow release rate of LPV was observed at about 20% on day 5, followed by a sustained release beyond 14 days. RTV released faster than LPV in the first 5 days and slower than LPV thereafter. LPV trough concentration remained above 160 ng/mL and RTV trough concentration was above 50 ng/mL after 6 days with one subcutaneous injection. Overall, the ISNP-based LPV/RTV injection showed sustained release profiles in both in vitro and in vivo studies.

scholarly journals A health worker knowledge, attitudes and practices survey of SARS-CoV-2 infection prevention and control in South Africa

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Saiendhra Vasudevan Moodley ◽  
Muzimkhulu Zungu ◽  
Molebogeng Malotle ◽  
Kuku Voyi ◽  
Nico Claassen ◽  
...  
Keyword(s):  
South Africa ◽  
Health Worker ◽  
Prevention And Control ◽  
Infection Prevention ◽  
Health Workers ◽  
Health Facilities ◽  
World Health ◽  
Infection Prevention And Control ◽  
Successful Implementation ◽  
And Control

Abstract Background Health workers are crucial to the successful implementation of infection prevention and control strategies to limit the transmission of SARS-CoV-2 at healthcare facilities. The aim of our study was to determine SARS-CoV-2 infection prevention and control knowledge and attitudes of frontline health workers in four provinces of South Africa as well as explore some elements of health worker and health facility infection prevention and control practices. Methods A cross-sectional study design was utilised. The study population comprised both clinical and non-clinical staff working in casualty departments, outpatient departments, and entrance points of health facilities. A structured self-administered questionnaire was developed using the World Health Organization guidance as the basis for the knowledge questions. COVID-19 protocols were observed during data collection. Results A total of 286 health workers from 47 health facilities at different levels of care participated in the survey. The mean score on the 10 knowledge items was 6.3 (SD = 1.6). Approximately two-thirds of participants (67.4%) answered six or more questions correctly while less than a quarter of all participants (24.1%) managed to score eight or more. A knowledge score of 8 or more was significantly associated with occupational category (being either a medical doctor or nurse), age (< 40 years) and level of hospital (tertiary level). Only half of participants (50.7%) felt adequately prepared to deal with patients with COVD-19 at the time of the survey. The health workers displaying attitudes that would put themselves or others at risk were in the minority. Only 55.6% of participants had received infection prevention and control training. Some participants indicated they did not have access to medical masks (11.8%) and gloves (9.9%) in their departments. Conclusions The attitudes of participants reflected a willingness to engage in appropriate SARS-CoV-2 infection prevention and control practices as well as a commitment to be involved in COVID-19 patient care. Ensuring adequate infection prevention and control training for all staff and universal access to appropriate PPE were identified as key areas that needed to be addressed. Interim and final reports which identified key shortcomings that needed to be addressed were provided to the relevant provincial departments of health.

scholarly journals Exposure-response analysis after subcutaneous administration of RBP-7000, a once-a-month long-acting Atrigel formulation of risperidone

2017 ◽  
Vol 83 (7) ◽  
pp. 1476-1498 ◽  
Author(s):  
Vijay Ivaturi ◽  
Mathangi Gopalakrishnan ◽  
Jogarao V. S. Gobburu ◽  
Weiyan Zhang ◽  
Yongzhen Liu ◽  
...  
Keyword(s):  
Subcutaneous Administration ◽  
Response Analysis ◽  
Exposure Response ◽  
Long Acting

Effective Therapy of Insulinoma by Using Long-Acting Somatostatin Analogue. A Case Report and Literature Review

2011 ◽  
Vol 120 (02) ◽  
pp. 68-72 ◽  
Author(s):  
A. Jawiarczyk ◽  
M. Bolanowski ◽  
J. Syrycka ◽  
G. Bednarek-Tupikowska ◽  
M. Kałużny ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Somatostatin Receptors ◽  
Subcutaneous Administration ◽  
Pancreatic Neuroendocrine Tumor ◽  
Somatostatin Analogue ◽  
Left Adrenal Gland ◽  
Glucose Levels ◽  
Long Acting ◽  
The Right

AbstractWe are reporting a case of 68-year-old woman with insulinoma, after a non-successful tumor surgery and a long-term diazoxide treatment. She had a lot of hypoglycemia cases, and a weight gain of 50 kg. An abdominal CT scan demonstrated a tumor 28 mm in the diameter, in the head of the pancreas. The patient did not agree for the repeated insulinoma surgery. Furthermore, we found a lesion in the left adrenal gland (14 mm in the diameter) and in the right lung (8 mm in the diameter). Pheochromocytoma was diagnosed on the basis of hypertension, elevated levels of normetanephrine in the 24-h urine collection, and an elevated level of norepinephrine in a plasma sample. After the left adrenal gland removal we observed lower blood pressure. Since we had revealed the presence of somatostatin receptors by the somatostatin receptors scintigraphy, we decided to control hypoglycemia by a monthly subcutaneous administration of the long-acting lanreotide. Because of higher glucose levels (300–400 mg/dl) we started an intense insulin therapy. Nowadays, the patient feels better, she has lost 20 kg of her body weight, and we have observed normal blood glucose levels during the long-term lanreotide treatment. We have noticed neither side effects nor hypoglycemic episodes and we have reduced the dose of insulin. The presented case can be an evidence of the effective treatment of the pancreatic neuroendocrine tumor of insulinoma type, with somatostatin analogue.

scholarly journals In vitro Release Kinetics Study of Ranolazine from Swellable Hydrophilic Matrix Tablets

1970 ◽  
Vol 8 (1) ◽  
pp. 31-38 ◽  
Author(s):  
Mohammad Nezab Uddin ◽  
Ishtiaq Ahmed ◽  
Monzurul Amin Roni ◽  
Muhammad Rashedul Islam ◽  
Mohammad Habibur Rahman ◽  
...  
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Release Kinetics ◽  
In Vitro Release ◽  
High Viscosity ◽  
Matrix Tablets ◽  
Release Studies ◽  
The Matrix ◽  
Vitro Release

The objective of this study was to design oral sustained release matrix tablets of Ranolazine usinghydroxypropyl methylcellulose (HPMC) as the retardant polymer and to study the effect of formulation factors suchas polymer proportion and polymer viscosity on the release of drug. In vitro release studies were performed usingUSP type II apparatus (paddle method) in 900 mL of 0.1N HCl at 100 rpm for 12 hours. The release kinetics wasanalyzed using the zero-order, first order, Higuchi and Korsmeyer-Peppas equations to explore and explain themechanism of drug release from the matrix tablets. In vitro release studies revealed that the release rate decreasedwith increase in polymer proportion and viscosity grade. Mathematical analysis of the release kinetics indicated thatthe nature of drug release from the matrix tablets was dependent on drug diffusion and polymer relaxation andtherefore followed non-Fickian or anomalous release. The developed controlled release matrix tablets of Ranolazineprepared with high viscosity HPMC extended release up to 12 hours.Key words: Ranolazine; Sustained release; Methocel E50 Premium LV; Methocel K100LV CR; Methocel K4M CR;Methocel K15M CR.DOI: 10.3329/dujps.v8i1.5333Dhaka Univ. J. Pharm. Sci. 8(1): 31-38, 2009 (June)

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