Sex differences in the pharmacokinetics and bioequivalence of the delayed-release combination of doxylamine succinate-pyridoxine hydrochloride; implications for pharmacotherapy in pregnancy.
J Clin Pharmacol
; 53(12): 1268-76, 2013 Dec.
Article
em En
| MEDLINE
| ID: mdl-24123059
Most bioequivalence (BE) studies are conducted in males with the assumption that variability in pharmacokinetics is similar between the sexes. The purpose of this single-center, reference replicate study was to determine the effect of sex on the pharmacokinetics and BE of doxylamine-pyridoxine 10 mg-10 mg delayed-release tablets. Healthy males (n = 12) and non-pregnant females (n = 12) were administered two tablets, and blood sampling was conducted from 1 hour pre-dose until 72 hours post-dose. After 21 days, dose administration and blood sampling were re-conducted. All analytes were measured using liquid chromatography-tandem mass-spectrometry. Pharmacokinetic parameters were calculated for each study period using standard, non-compartmental methods, and differences were assessed using ANOVA. BE testing was conducted using the relative 90% confidence interval for the AUC0-t for each analyte. Females had significantly larger AUC0-t for doxylamine, 1,550 ng h/mL (coefficient of variance [CV = 19%]) versus 1,272 ng h/mL (CV = 21%; P ≤ .05), and pyridoxine, 35 ng h/mL, (CV = 43%) versus 25 ng h/mL (CV = 31%; P ≤ .05) compared to males. A higher Cmax for doxylamine was observed in females, 107 ng/mL (CV = 16%), compared to males, 86 ng/mL (CV = 15%) (P ≤ .05). BE testing did not demonstrate bioequivalence between males and females. Pharmacokinetic differences observed between the sexes have implications for future BE studies using doxylamine-pyridoxine.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piridoxina
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Diciclomina
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Doxilamina
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Antieméticos
Limite:
Adult
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Female
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Humans
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Male
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Pregnancy
Idioma:
En
Revista:
J Clin Pharmacol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Canadá
País de publicação:
Reino Unido