Bioequivalence of two enteric coated formulations of pantoprazole in healthy volunteers under fasting and fed conditions.
OBJECTIVE
To compare the bioavailability of two pantoprazole (CAS 102625-70-7) formulations (40 mg pantoprazole enteric coated tablets) under fasted and fed conditions as well as to evaluate the dissolution profile in biorelevant media.


METHODS
The subjects received either 40 mg of the reference or of test formulation in fasting (n = 28) and fed (n=70) condition. The studies were conducted according to a single dose and randomized crossover design. Blood samples were collected up to 12 h after drug administration in fasting condition and up to 48 h in fed condition. Plasma concentrations of pantoprazole were determined by LC-MS/MS. Pharmacokinetic parameters were calculated from the observed plasma concentration-time profiles. Bioequivalence between the formulations in fasting and fed condition was assessed considering 90% confidence intervals for the ratio of means for lnCmax and lnAUC(0-t) within 0.8-1.25. Dissolution profiles were evaluated in biorelevant media [Fasting State Simulating Intestinal Fluid (FaSSIF) and Fed State Simulating Intestinal Fluid (FeSSIF)]. The sameness of the dissolution curves was assessed by f2 values between 50 and 100.


RESULTS
Under fasting condition the 90% confidence interval for the ratio of means for the lnCmax, (0.94-1.03) and lnAUC(0-t) (0.89-0.99) was within the guideline range of bioequivalence (0.80-1.25). However, the data for lnCmax (0.51-0.76) and lnAUC(0-t) (0.68-0.90) under fed condition were not within the bioequivalence range. The postprandial study demonstrated a high intra-subject variability and in some subjects pantoprazole could not be detected for up to 24 h, although the dissolution profile of reference and test formulations presented a similar disposition in FaSSIF and FeSSIF as confirmed by the values of f2 higher than 50.


CONCLUSIONS
The results demonstrated that the test formulation was bioequivalent to the reference in fasting condition but not in postprandial state. The dissolution profile in FaSSIF indicates that this biorelevant medium was more adequate to discriminate the in vivo disposition of pantoprazole than FeSSIF. Furthermore, the fed condition study had shown a pronounced influence of food in the absorption of pantoprazole after single oral dose administration.
Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Bragança Paulista, SP (Brazil). cinetica04@yahoo.com.br
Daniel Rossi
DR
de Campos
Nelson Rogério
NR
Vieira
Gilberto
G
Bernasconi
Fabio Alessandro Proença
FA
Barros
Eduardo César
EC
Meurer
Marco Antônio
MA
Marchioretto
Edvaldo Capobiango
EC
Coelho
Silvana Aparecida
SA
Calafatti
Carolina
C
Sommer
Jussara Moreira
JM
Couto
Simoni
S
Buranello
Andréia Rodrigues Cristino
AR
Silva
Antônio Ricardo
AR
Amarante
Eduardo
E
Abib
José Pedrazzoli
JP
Júnior
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000897:Anti-Ulcer Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D005079:Excipients; D005215:Fasting / Q000502:physiology; D006801:Humans; D013058:Mass Spectrometry; D000077402:Pantoprazole; D012995:Solubility; D013608:Tablets, Enteric-Coated; D013810:Therapeutic Equivalency
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D005079:Excipients; D013608:Tablets, Enteric-Coated; D000077402:Pantoprazole