Systemic bioavailability and pharmacokinetics of the doxylamine-pyridoxine delayed-release combination (diclectin)

Simerpal Kaur Gill, Facundo Garcia-Bournissen, Gideon Koren

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Background: Diclectin, composed of 10 mg doxylamine succinate (DOX) and 10 mg pyridoxine hydrochloride, is the drug combination of choice for the management of nausea and vomiting during pregnancy in Canada. However, there is large variability in its onset and duration of action among women. To understand and improve its effectiveness, the variability in the pharmacokinetics of the ingredients in this doxylamine succinate/pyridoxine hydrochloride combination must be studied. Objectives: To determine the pharmacokinetics of DOX and pyridoxine after oral administration of two tablets of this drug combination in the form of Diclectin and to calculate their respective relative bioavailability by comparison with intravenous administration in another population. Methods: Eighteen nonpregnant, nonlactating, healthy females between 18 and 45 years of age were administered two tablets of Diclectin with 240 mL of water under empty stomach conditions. Blood samples were analyzed for DOX and pyridoxine along with its four active metabolites: pyridoxal, pyridoxal-5′-phosphate (PLP), pyridoxamine, and pyridoxamine-5′-phosphate using tandem mass spectrometry. For the purpose of this study, pharmacokinetic values for DOX and PLP were adjusted for body weight. Results: The mean DOX-AUC0→∞ was calculated to be 3137.22 ± 633.57 ng•hr/mL (range, 2056.59-4376.06 ng•hr/mL). The mean PLP-AUC0→∞ was calculated to be 5513.10 ± 2362.35 ng•hr/mL (range, 1572.56-10,153.77 ng•hr/mL). Based on literature values of the PLP-AUC0→∞ after intravenous administration and data from the current study, the relative bioavailability of pyridoxine in Diclectin was calculated at 100%. Conclusion: There was a 2.1-fold variability in the DOX-AUC0→∞ and 6.5-fold variability in the PLP-AUC0→∞ after oral administration of 20 mg Diclectin. Using literature values and data from the current study, we estimated the oral bioavailability of pyridoxine to be 100%. Therefore, interindividual differences in metabolism, and not in bioavailability, may be important sources of variability that need to be addressed in dosing guidelines.

Original languageEnglish
Pages (from-to)115-119
Number of pages5
JournalTherapeutic Drug Monitoring
Issue number1
StatePublished - Feb 2011
Externally publishedYes


  • Diclectin
  • doxylamine succinate
  • pharmacokinetics
  • pyridoxal-5'-phosphate
  • pyridoxine
  • therapeutic drug monitoring


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