Bio-équivalence et génériques de principes actifs à marge thérapeutique étroite

Corre, Pascal Le

doi:10.1016/j.lpm.2009.09.017

Cited by 12 publications

(3 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In man, ciclosporin has a <2-fold difference between the minimum toxic concentration and minimum effective concentration in blood [ 17 , 18 ], and the debate as to whether or not it is necessary to apply stricter guidelines for such narrow therapeutic index drugs has been ongoing for several decades in human health. Indeed, it has been suggested that the usual acceptance interval for AUC and Cmax may need to be tightened to 90 % to 112 % for such drugs, but there is currently no international consensus on the subject [ 17 , 18 ]. However, even if the pharmacokinetic properties of ciclosporin are very similar in dogs and man, its safety margin is much wider in dogs [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

“…In human health, the scientific aspects of bioequivalence that govern the use of generics are sometimes described ambiguously in the literature, and they are therefore not always perceived clearly by health professionals. This lack of clarity may be an obstacle to their use [ 17 ]. However, according to the US Food and Drug Administration [ 19 ], if a drug product contains a drug substance that is chemically identical and is delivered to the site of action at the same rate and extent as another drug product, then it is equivalent and can be substituted (switchable) for that drug product.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Bioequivalence study between two formulations of ciclosporin A (Cyclavance® oral solution and Atopica® soft capsules) following a single oral administration to dogs

Navarro

Séguy

Vila³

et al. 2016

BMC Vet Res

View full text Add to dashboard Cite

BackgroundCiclosporin is a selective immunomodulator used for the treatment of atopic dermatitis in dogs. A new 100 mg/ml oral solution formulation (Cyclavance®, Virbac) was developed as a pharmaceutical equivalent to the marketed capsule formulations (Atopica®, Novartis Animal Health) containing 25, 50 mg, or 100 mg of ciclosporin A. The aim of this study was to assess and compare the pharmacokinetic profiles and bioequivalence of the two formulations following a single oral administration to dogs. This randomised, two-period, two-sequence, crossover bioequivalence study was conducted in 40 healthy dogs under fasting conditions. Each dog received either one 50 mg capsule of Atopica® or 0.5 ml of Cyclavance®. After dosing, blood samples were collected during a 48-h time period at 0, 0.5, 1, 2, 4, 6, 12, 24, 36 and 48 h. Blood ciclosporin A concentrations were measured by using an HPLC-MS/MS method. Cmax, Tmax, t1/2, AUC0-t, AUC0-∞ and Kel were determined for the two ciclosporin formulations. Bioequivalence was to be concluded if the 90 % confidence intervals were within the range of 80 % to 125 % for Cmax and AUC0-t. Dogs were monitored once daily throughout the study period for adverse effects.ResultsThe 90 % confidence intervals for Cyclavance®/Atopica® mean ratios of the log-transformed pharmacokinetic variables Cmax and AUC0-t were within the conventional bioequivalence range of 80 % to 125 % (Point estimate: 101.2 % and 101.4 % respectively). Except for salivation reported after administration of both products, or vomiting and diarrhoea reported after Atopica® administration, both formulations were well tolerated in the 40 healthy dogs over the 48-h study period.ConclusionsThe two ciclosporin oral formulations demonstrated similar pharmacokinetic profiles and were found to be bioequivalent, and therefore, interchangeable.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bioequivalence study between two formulations of ciclosporin A (Cyclavance® oral solution and Atopica® soft capsules) following a single oral administration to dogs

Navarro

Séguy

Vila³

et al. 2016

BMC Vet Res

View full text Add to dashboard Cite

show abstract

“…The establishment of BE is particularly crucial when considering medicines with highly toxic ingredients or in a Narrow Therapeutic Range (NTR), i.e., where small differences in dosage can have toxic effects. National regulatory authorities have discretion to define how to measure a product’s NTR, and also, to determine which medicines require BE testing (7). These are decisions each country must make for itself.…”

Section: Dimensions Of Analysismentioning

confidence: 99%

Promoting and regulating generic medicines: Brazil in comparative perspective

Fonseca

Shadlen

2017

Revista Panamericana De Salud Pública

View full text Add to dashboard Cite

Promoting the use of generic drugs can constitute a core instrument for countries’ national pharmaceutical policies, one that reduces drug expenditure while expanding health care access. Despite the potential importance of such policy measures and the differences among national practices, scholars embarking on comparative analysis lack a roadmap for determining which dimensions of generic drug policy to assess and compare. This report fills that gap by considering national rules and regulations across four dimensions deemed crucial to any evaluation: demonstrated therapeutic equivalence; pharmaceutical packaging and labeling; drug prescription; and drug substitution. Furthermore, this report examines how the diverse interests of public and private sector stakeholders might shape generic drug policy and its implementation. To illustrate the challenges and conflicts behind policy development and implementation, this report focuses on the case of Brazil.

show abstract