scholarly journals Real-World Experience with Carbidopa-Levodopa Extended-Release Capsules (Rytary®): Results of a Nationwide Dose Conversion Survey

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Robert A. Hauser ◽  
Ghazal Banisadr ◽  
Kara Vuong ◽  
David Freilich ◽  
Stanley Fisher ◽  
...  
Keyword(s):  
Extended Release ◽  
Symptom Control ◽  
Critical Role ◽  
Immediate Release ◽  
Primary Objective ◽  
Multiple Choice Questions ◽  
Conversion Period ◽  
Conversion Table ◽  
Starting Point ◽  
Practice Methods

Background. The introduction of carbidopa-levodopa extended-release (CD-LD ER) capsules (Rytary®) did not go as smoothly as expected, largely due to difficulty around dose conversion from available immediate-release (IR) levodopa (LD) formulations. The dose conversion table in the CD-LD ER prescribing information was similar to the table used in the pivotal clinical trial and is considered by many prescribing HCPs to be less than optimal. By the end of the dose conversion period in that trial, dosing in 76% of subjects was adjusted for symptom control; roughly 60% of patients required a higher dose and about half required more frequent administration than the recommended TID dosing. Objective. The primary objective of our nationwide (US) survey was to determine the dose conversion strategy most commonly employed by CD-LD ER frequent prescribers. The survey also aimed to explore additional features regarding CD-LD ER use in clinical practice. Methods. A survey consisting of 21 multiple-choice questions was developed and administered to experts in the use of CD-LD ER, based on prescription volume. Results. Of the 394 HCPs who were invited to participate, 90 (23%) HCPs completed the survey. All respondents were aware of the dose conversion table; the largest group did not find the table to be helpful and did not use it to convert patients to CD-LD ER. The most common strategy in calculating the CD-LD ER dose was based on the total daily LD IR dose, with the majority of that group initiating dose conversion by doubling the total daily LD dose from CD-LD IR and administering CD-LD ER one less time per day. Conclusion. Overall, most survey respondents agreed that a good starting point for CD-LD ER conversion could be doubling the daily LD IR dose and administering it one time less frequently. Moreover, rapid patient follow-up after initial dose conversion to allow for further dose adjustments plays a critical role in achieving success. Gaining experience over time is important for satisfactory conversion.

scholarly journals Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study

2016 ◽  
Vol 60 (4) ◽  
pp. 2492-2498 ◽  
Author(s):  
Marcelo Gomes Davanço ◽  
Michel Leandro Campos ◽  
Talita Atanazio Rosa ◽  
Elias Carvalho Padilha ◽  
Alejandro Henao Alzate ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Extended Release ◽  
Hydroxypropyl Methylcellulose ◽  
Immediate Release ◽  
Relative Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Success ◽  
Preclinical Pharmacokinetics ◽  
Bioavailability Study

ABSTRACTBenznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediate-release tablets for 100-mg (adult) and 12.5-mg (pediatric) doses. The drug is administered two or three times daily for 60 days. The high frequency of daily administrations and the long period of treatment are factors that significantly contribute to the abandonment of therapy, affecting therapeutic success. Accordingly, this study aimed to evaluate the preclinical pharmacokinetics of BNZ administered as extended-release tablets (200-mg dose) formulated with different types of polymers (hydroxypropyl methylcellulose K4M and K100M), compared to the tablets currently available. The studies were conducted with rabbits, and BNZ quantification was performed in plasma and urine by ultraperformance liquid chromatography methods previously validated. The bioavailability of BNZ was adequate in the administration of extended-release tablets; however, with the administration of the pediatric tablet, the bioavailability was lower than with other tablets, which showed that the clinical use of this formulation should be monitored. The pharmacokinetic parameters demonstrated that the extended-release tablets prolonged drug release from the pharmaceutical matrix and provided an increase in the maintenance of the drug concentrationin vivo, which would allow the frequency of administration to be reduced. Thus, a relative bioavailability study in humans will be planned for implementation of a new product for the treatment of Chagas disease.

scholarly journals Isolated domains of recombinant human apo-metallothionein 1A are folded at neutral pH: a denaturant and heat-induced unfolding study using ESI-MS

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Gordon W. Irvine ◽  
Natalie Korkola ◽  
Martin J. Stillman
Keyword(s):  
Critical Role ◽  
Cysteine Residues ◽  
Small Molecular Weight ◽  
Esi Ms ◽  
Neutral Ph ◽  
Induced Folding ◽  
Starting Point ◽  
High Metal ◽  
High Concentrations ◽  
Product Species

Metallothioneins (MTs) are characterized by their high metal loading capacity, small molecular weight, and abundant cysteine residues. It has long been thought that metal-free, or apo-MT peptides were unstructured and only adopted as a distinct conformation upon forming the metal clusters, described as metal-induced folding. More recent studies have suggested that the presence of a globular, yet loosely defined structure actually exists that can be disrupted or unfolded. Residue modification and ion-mobility ESI (IM-ESI)-MS have been used to examine this unusual unfolding process. The structure of apo-MT plays a critical role as the starting point in the flexible metalation pathways that can accommodate numerous soft metals. ESI-MS measurements of the product species formed following the cysteine alkylation of the isolated domain fragments of recombinant human apo-MT 1A with n-ethylmaleimide (NEM) were used in the present study to monitor the denaturant- and heat-induced unfolding at physiological pH. The results indicate that these apo-MT fragments adopt distinct structures at neutral pH that react co-operatively with NEM when folded and non-cooperatively when heated or exposed to high concentrations of the denaturant guanidinium chloride (GdmCl). From these studies, we can conclude that at neutral pH, the domain fragments are folded into globular structures where some of the free cysteine residues are buried within the core and are stabilized by hydrogen bonds. Metalation therefore, must take place from the folded conformation.

Steady-state pharmacokinetic profile of OROS hydromorphone extended release and hydromorphone immediate release

2010 ◽  
Vol 11 (4) ◽  
pp. S44
Author(s):  
K. Moore ◽  
D. St. Fleur ◽  
N. Marricco ◽  
T. Ariyawansa ◽  
V. Page ◽  
...  
Keyword(s):  
Steady State ◽  
Extended Release ◽  
Immediate Release ◽  
Pharmacokinetic Profile

scholarly journals PAR5 COST-EFFECTIVENESS OF EXTENDED-RELEASE AND IMMEDIATE-RELEASE TRAMADOL FOR THE TREATMENT OF CHRONIC OSTEOARTHRITIS PAIN

2007 ◽  
Vol 10 (3) ◽  
pp. A118 ◽  
Author(s):  
AD Patkar ◽  
P Langley ◽  
C Janagap ◽  
K Meyer ◽  
A Grogg ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Extended Release ◽  
Immediate Release ◽  
Osteoarthritis Pain
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