scholarly journals Tacrolimus Intrapatient Variability After Switching From Immediate or Prolonged-Release to Extended-Release Formulation, After an Organ Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Arnaud Del Bello ◽  
Clotilde Gaible ◽  
Nathalie Longlune ◽  
Anne-Laure Hebral ◽  
Laure Esposito ◽  
...  

Background and Purpose: Several formulations of tacrolimus are available, but evidence of the benefit of changing to the most recent formulations is lacking. Tacrolimus intra-patient variability (tacrolimus IPV) is an emerging risk factor associated with poor graft outcomes after solid organ transplantations. Here, we examined the modifications of tacrolimus IPV after switching to a different formulation of tacrolimus.Experimental Approach: We identified 353 solid organ transplant recipients that were switched in our center from immediate-release (IR-tacrolimus) or prolonged-release tacrolimus (PR-tacrolimus) to extended-release, LCP-tacrolimus (LCP-tacrolimus). Among them, 54 patients underwent at least 3 available tacrolimus blood concentrations before and after the switch, allowing us to investigate tacrolimus IPV.Key Results: The switch was considered as a safe procedure since only four of the 353 patients presented a graft rejection after the switch, and no patient was hospitalized for tacrolimus overdose. The tacrolimus IPV estimated by the coefficient of variation (CV-IPV) was stable before and after the switch to LCP-tacrolimus (CV-IPV: 29.0% (IQR 25–75 (15.5; 38.5) before and 24.0% (15.8; 36.5) after the switch, p = 0.65).Conclusion and Implications: Switching from IR- or PR-tacrolimus to LCP-tacrolimus is a safe procedure. However, the CV-tacrolimus IPV was not impacted by the change of formulation.

2005 ◽  
Vol 21 (4) ◽  
pp. 483-487 ◽  
Author(s):  
Jeremy P. Hing ◽  
Vladimir Piotrovsky ◽  
Hui Kimko ◽  
H. Robert Brashear ◽  
Qinying Zhao

2011 ◽  
Vol 3 ◽  
pp. JCNSD.S5210 ◽  
Author(s):  
Paul S. Fishman

Pramipexole has been a widely used dopamine agonist for the last decade. Recently an extended release formulation of pramipexole has been introduced as both monotherapy for patients with early Parkinson's disease as well as for patients with more advanced disease, as an adjunct to L-DOPA. Along with the enhanced patient compliance seen with once a day dosing, there are other potential advantages of extended release preparations of dopamine agonists. Patients initiated on pramipexole have a lower incidence of developing motor fluctuations including dyskinesia than those initiated on L-DOPA. Pramipexole requires a prolonged dose titration compared to L-DOPA, and generally does not have the efficacy of L-DOPA. The extended release form of pramipexole shows comparable mean and peak serum levels with once a day dosing as seen with three times a day dosing of the immediate release preparation. The extended release preparation has been studied in randomized multicenter clinical trial against both placebo and the immediate release preparation in the setting of early Parkinson's disease as monotherapy and in more advanced patients with motor fluctuations on L-DOPA. In both settings the extended release preparation was superior to placebo and comparable to the immediate release form in efficacy with a similar side effect profile including nausea, sleepiness, leg edema, dyskinesias, hallucinations and impulse control disorders.


2011 ◽  
Vol 3 ◽  
pp. JCNSD.S4126
Author(s):  
Hasan H. Sonmezturk ◽  
Nabil J. Azar

Extended release (XR) formulation of levetiracetam (LEV) is approved by the Food and Drug Administration as an add-on to other antiepileptic drugs (AEDs) for adults with partial onset seizures. This is based on class-I evidence demonstrating significant seizure reduction in once daily dosing. Keppra-XR is marketed with the brand name of Keppra XR since 2008 (UCB Pharma). Its original immediate release (IR) formulation has been in the market since 2000. LEV has a unique molecular structure which is chemically unrelated to existing AEDs. The precise mechanism of action is unknown. Animal studies showed binding to synaptic vesicle protein SV2A, thought to be involved in modulating synaptic neurotransmitter release. LEV-IR is proven effective as adjunctive therapy for partial-onset seizures, primary generalized tonic-clonic seizures and myoclonic seizures. It was shown to be equivalent to carbamazepine as first-line treatment for partial-onset seizures. The extended release formulation added advantages such as better tolerance and increased compliance.


2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Wolfram Eisenreich ◽  
Bernd Sommer ◽  
Sebastian Hartter ◽  
Wolfgang H. Jost

Pramipexole, the most commonly prescribed dopamine agonist worldwide, meanwhile serves as a reference substance for evaluation of new drugs. Based on numerous clinical data and vast experiences, efficacy and safety profiles of this non-ergoline dopamine agonist are well characterized. Since October 2009, an extended-release formulation of pramipexole has been available for symptomatic treatment of Parkinson's disease. Pramipexole administration can be cut down from three times to once a day due to the newly developed extended-release formulation. This is considerable progress in regard to minimizing pill burden and enhancing compliance. Moreover, the 24 h continuous drug release of the once-daily extended-release formulation results in fewer fluctuations in plasma concentrations over time compared to immediate-release pramipexole, given three times daily. The present study summarizes pharmacokinetics and all essential pharmacological and clinical characteristics of the extended-release formulation. In addition, it provides all study data, available so far, with regard to transition and de-novo administration of extended-release formulation for patients with Parkinson's disease. It further compares efficacy and safety data of immediate-release pramipexole with the extended-release formulation of pramipexole.


Author(s):  
SAIYED ZEYAUL ABRAR HUSAIN ◽  
ARSHAD KHUROO ◽  
AMIT MARWAH ◽  
DIVYA VOHORA

Objective: This study was designed to assess the pharmacokinetics of single dose of olopatadine hydrochloride 10 mg extended release (ER) tablet of Ranbaxy laboratories limited (two test formulations) with two doses of Allelock® 5 mg immediate release (IR) tablets of Kyowa Hakko Kogyo Co. Ltd. (reference formulation R), in healthy, adult, Indian male subjects under fed condition. Methods: Fifteen healthy male volunteers, 26.07±6.62 y in age and 57.17±6.68 kg in body weight, were divided into three groups and received either olopatadine hydrochloride 10 mg ER tablet or two doses of Allelock® 5 mg tablets in each period. Blood samples were taken at predetermined time points and plasma concentrations of olopatadine were monitored by liquid chromatography mass spectrometric (LCMS/MS). Pharmacokinetic (PK) parameters AUC0-t, AUC0-24, AUC0-∞, and Cmax were calculated for olopatadine using WinNonlin. A statistical analysis was performed on PK data using SAS system. Results: The ER formulations showed a similar AUC as compared to the IR formulation and there was no statistically significant difference in AUC of test formulation A and B and reference R. The ratios of AUC0-t, AUC0-24 and AUC0-∞ for A/R were 91.08, 94.90 and 91.32 and for B/R were 89.63, 93.95 and 89.63 respectively. The ER formulations reported a higher Cmax value as compared to IR formulation. The ratios of Cmax for A/R and B/R were 151.09 and 167.96 respectively. But these higher Cmax values did not pose any safety issue as there were no serious adverse events reported during the study. Conclusion: In conclusion, we can say that though the study drugs did not meet the bioequivalence criteria set by regulatory agencies, but this study gave an insight about PK properties of olopatadine extended release formulation and given an idea about effect of smoking on the PK profile of olopatadine which can be studied in future.


2021 ◽  
Vol 74 (4) ◽  
Author(s):  
Wen-Yuan Johnson Kuan ◽  
Nathalie Châteauvert ◽  
Vincent Leclerc ◽  
Benoît Drolet

Background: Tacrolimus may be administered during hospitalization as an IV formulation or oral suspension. However, literature suggesting appropriate ratios for conversion from these formulations to capsules is limited. Objective: To evaluate conversion ratios after a switch in formulation of tacrolimus for solid-organ transplant recipients. Methods: This single-centre observational longitudinal study involved hospitalized patients who underwent a switch in formulation of tacrolimus according to 1 of 3 possible scenarios: IV to oral suspension, IV to capsule, or oral suspension to capsule. Data were collected from the earliest accessible electronic file (January 2009) to January 1, 2019. Conversion ratios were calculated for each of the 3 groups using data for blood concentrations and doses before and after the switch. The calculated ratios were then compared with recommended conversion ratios: 1:5 (i.e., 1 mg of IV tacrolimus is converted to 5 mg of oral tacrolimus, expressed as “5”) for either of the switches involving an IV formulation and 1:1 (i.e., same amount, expressed as “1”) for the switch from oral formulation to capsules. Results: For the group who underwent switching from the IV formulation to oral suspension, the mean calculated conversion ratio was 3.04, which was significantly different from the recommended ratio of 5. For the group who underwent switching from the IV formulation to capsules, the calculated conversion ratio was 5.18, which was not significantly different from the recommended ratio of 5. For the group who underwent switching from oral suspension to capsules, the calculated conversion ratio was 1.17, which was not significantly different from the recommended ratio of 1. Conclusion: In this small retrospective study of tacrolimus therapy, the calculated conversion ratio was significantly different from the recommended ratio for patients who were switched from IV administration to oral suspension, but not for those switched from IV administration or oral suspension to capsules. Therapeutic drug monitoring therefore appears indispensable, regardless of conversion ratios. RÉSUMÉ Contexte : Le tacrolimus peut être administré par IV ou sous forme de suspension orale pendant une hospitalisation. Cependant, il existe peu de documents qui proposent des ratios appropriés pour convertir ces formulations en capsules. Objectif : Évaluer les ratios de conversion après un changement de formulation du tacrolimus pour les bénéficiaires de greffes d’organes solides. Méthodes : Cette étude observationnelle longitudinale unicentrique impliquait des patients hospitalisés, pour qui la formulation de tacrolimus changeait en fonction de chacun des trois scénarios possibles : passage de l’administration par IV à la suspension orale, passage de l’administration par IV aux capsules ou passage de l’administration par suspension aux capsules. Le recueil des données a été effectué à partir du plus ancien dossier électronique accessible (janvier 2009) jusqu’au 1er janvier 2019. Les ratios de conversion ont été calculés pour chacun des trois groupes à l’aide de données pour les concentrations de sang et des doses avant et après le changement. Les ratios calculés ont ensuite été comparés avec les ratios de conversion recommandés : 1:5 (c.-à-d., 1 mg de tacrolimus administré par IV est converti en 5 mg de tacrolimus par voie orale, conversion exprimée par le nombre « 5 ») pour chacun des changements impliquant une formulation IV et 1:1 (c.-à-d. même quantité, conversion exprimée par le nombre « 1 ») pour le passage de la formulation orale aux capsules. Résultats : Dans le groupe dont l’administration par IV est passée à une suspension orale, le ratio de conversion moyen calculé était de 3,04, ce qui était significativement différent par rapport au ratio recommandé de 5. Pour le groupe dont l’administration par IV est passée à des capsules, le ratio de conversion moyen calculé était de 5,18, ce qui n’était pas significativement différent par rapport au ratio recommandé de 5. Pour le groupe dont l’administration est passée de la suspension orale aux capsules, le ratio de conversion moyen calculé était de 1,17, ce qui n’était pas significativement différent par rapport au ratio recommandé de 1. Conclusion : Dans cette petite étude rétrospective de la thérapie à l’aide du tacrolimus, le ratio de conversion calculé était significativement différent du ratio recommandé pour les patients qui passaient d’une administration IV à une suspension orale, mais pas pour ceux qui passaient d’une administration par IV ou d’une suspension orale à des capsules. La surveillance thérapeutique des médicaments semble donc indispensable, quels que soient les ratios de conversion.


Sign in / Sign up

Export Citation Format

Share Document