PHARMACOKINETIC COMPARISON OF A DELAYED- RELEASE COMBINATION OF DOXYLAMINE SUCCINATE AND PYRIDOXINE HYDROCHLORIDE (DICLECTIN?) AND ORAL SOLUTIONS OF THESE DRUGS IN HEALTHY WOMEN OF CHILDBEARING AGE
Main Article Content
Keywords
Nausea and vomiting of pregnancy, pregnancy, pharmacokinetics, doxylamine succinate, pyridoxine chloride, pyridoxal, pyridoxamine, pyridoxal-5 phosphate
Abstract
Background
The delayed-release combination of doxylamine succinate and pyridoxine hydrochloride was the most commonly used antiemetic (Bendectin) approved by FDA for nausea and vomiting of pregnancy (NVP) until its removal of the market in 1983. The drug is widely used today in Canada (Diclectin?). The pharmacokinetics of Diclectin? has never been described in humans.
Objectives
To compare the pharmacokinetics of Diclectin? to oral solutions of its two components.
Subjects and Methods
A randomized, cross over, open label design, comparing the pharmacokinetics of Diclectin? to those of the oral solutions of the two components in 18 healthy adult, non pregnant women of childbearing age.
Results
Diclectin? exhibited similar oral bioavailability to those of the oral solutions. In contrast, the time-topeak, (Tmax), reflecting the rate of absorption, was 3-6 times longer for the two components of the delayed-release drug confirming its delayed-release characteristics.
Conclusion
The pharmacokinetic profile of Diclectin? well explains its documented delayed efficacy.
References
2. Levichek Z, Atanackovic G, Oepkes D, Maltepe C, Einarson A, Magee L, Koren G. Nausea and vomiting of pregnancy. Evidence-based treatment algorithm. Can Fam Physician 2002 Feb; 48:267-8, 277.
3. Magee LA, Mazzotta P, Koren G. Evidencebased view of safety and effectiveness of pharmacologic therapy for nausea and vomiting of pregnancy (NVP). Am J Obstet Gynecol. 2002 May; 186(5):S256-61.
4. Bishai R, Mazzotta P, Atanackovic G, Levichek Z, Pole M, Magee LA, Koren G. Critical appraisal of drug therapy for nausea and vomiting of pregnancy: II. Efficacy and safety of diclectin (doxylmaine-B6). Can J Clin Pharmacol. 2000 Autumn; 7(3):138-43.
5. Brent RL. Bendectin: review of the medical literature of a comprehensively studied human nonteratogen and the most prevalent tortogenlitigen. Reprod Toxicol. 1995; 39337-49.
6. Brent R. Bendectin and birth defects: hopefully, the final chapter. Birth Defects Res A Clin Mol Teratol. 2003 Feb; 67(2):79-87.
7. Ornstein M, Einarson A, Koren G. Bendectin/diclectin for morning sickness; a Canadian follow-up of an American tragedy Reprod Toxicol. 1995 Jan-Feb; 9(1):1-6.
8. Boskovic R, Einarson A, Maltepe C, Wolpin J, Koren G. Diclectin therapy for nausea and vomiting of pregnancy: effects of optimal dosing. J Obstet Gynaecol Can. 2003 Oct; 25(10):830-3.
9. Koren G, Maltepe C. Pre-emptive therapy for severe nausea and vomiting of pregnancy and hyperemesis gravidarum. J Obstet Gynaecol. 2004 Aug; 24(5):530-3.
10. Atanackovic G, Navioz Y, Moretti ME, Koren G. The safety of higher than standard dose of doxylamine-pyridoxine (Diclectin) for nausea and vomiting of pregnancy. J Clin Pharmacol. 2001 Aug; 41(8):842-5.