Comparison of Pharmacokinetic Profiles of Brand-Name and Generic Formulations of Citalopram and Venlafaxine
Notice bibliographique
Résumé
BACKGROUND: Generic drugs are lower-cost versions of patent-expired brand-name medications. Bioequivalence is decreed when the 90% confidence intervals for the ratios of the generic to the reference compound for the area under the curve and maximum plasma concentration (C(max)) fall within a 0.80 to 1.25 range. The aim of the present pilot study was to compare the pharmacokinetic profiles of brand-name and generic formulations of citalopram and extended-release venlafaxine. METHOD: Effexor XR/Novo-venlafaxine XR 75 mg and Celexa/Gen-citalopram 40 mg were studied in a randomized crossover design. Healthy male volunteers took either Effexor XR or Novo-venlafaxine XR for 4 days, a 4-day washout was allowed, and then participants took the other venlafaxine formulation for 4 days. This was followed by a washout of at least 7 days. The participants then took Celexa or Gen-citalopram for 8 days, a 14-day washout was allowed, and then participants took the other citalopram formulation for 8 days. In each of the study phases, the sequence of treatment (brand-name x generic) was randomly assigned. Plasma levels of drugs were measured at fixed intervals after participants took the drugs and at steady state. The study was conducted from November 2007 through July 2008. RESULTS: Twelve participants completed the venlafaxine study. Nine of the participants, plus 3 new participants, were then enrolled in the citalopram study, to maintain a total of 12. The plasma levels of citalopram were similar after ingestion of the brand-name and generic drugs. After ingestion of venlafaxine, the C(max) values were 36 +/- 6 ng/mL and 52 +/- 8 ng/mL in the brand-name and generic groups, respectively. The ratio of the log-transformed values of C(max) was 150% and, therefore, not within the acceptable 80% to 125% range. The concentration of the active metabolite of venlafaxine (O-desmethyl-venlafaxine [ODV]) was also significantly increased in the generic group (+43% higher in the generic group at 3 h; +48% higher at 5 h; p < .05). No differences were seen at steady state for either ODV or venlafaxine. Participants taking Novo-venlafaxine reported 3 times more side effects than those taking Effexor XR. Pill contents were identical in the 2 groups, but extraction of venlafaxine occurred more readily with the generic formulation than with the brand-name formulation, which required an additional sonication. CONCLUSION: Gen-citalopram appeared to be bioequivalent to Celexa, whereas Novo-venlafaxine XR was not bioequivalent to Effexor XR. Consequently, the Novo-venlafaxine formulation released its active ingredient more rapidly and outside the acceptable norm. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00676039.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».