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Clinical Pharmacology and Therapeutics 1967
Clinical Trial Comparative Study
Topics: Adult; Aged; Clinical Trials as Topic; Female; Histamine H1 Antagonists; Humans; Hypnotics and Sedatives; Male; Middle Aged; Secobarbital; Sleep Wake Disorders
PubMed: 4380998
DOI: 10.1002/cpt196781part148 -
Toxicology and Applied Pharmacology Dec 1996The effects of doxylamine (as the succinate salt) on microsomal enzyme activity and serum thyroid hormone levels were examined in B6C3F1 mice following dietary exposure...
The effects of doxylamine (as the succinate salt) on microsomal enzyme activity and serum thyroid hormone levels were examined in B6C3F1 mice following dietary exposure for 7 or 15 days (0, 40, 375, 750, or 1500 ppm in diet, expressed as free base doxylamine). In addition, the hepatic P450 enzyme inducer sodium phenobarbital (375 ppm, expressed as free acid phenobarbital) was used as a positive control for CYP2B induction. Exposure of mice to doxylamine produced dose-related increases in liver weight at both time points. Liver weights were also increased in the phenobarbital-treated mice. Doxylamine treatment caused a dose-dependent increase (up to 2.6-fold) in liver microsomal cytochrome P450 in both male and female mice, at both time points. Analyses of the activities of various hepatic microsomal cytochromes P450 indicated that doxylamine caused a marked induction of CYP2B enzymes. This was demonstrated by a large increase in the O-dealkylation of 7-pentoxyresorufin (up to 38-fold) and the 16beta-hydroxylation of testosterone (up to 6.9-fold), both of which are indicative of CYP2B induction. In addition, like phenobarbital, doxylamine treatment resulted in a modest induction of CYP3A and CYP2A enzymes and approximately a 50% increase in thyroxine-glucuronosyltransferase activity. Doxylamine did not appear to induce P450 enzymes in the CYP1A, CYP2E, or CYP4A enzyme subfamilies. None of the enzyme-inducing effects of doxylamine could be distinguished from those of phenobarbital. These results suggest that doxylamine is a phenobarbital-type inducer of liver microsomal cytochrome P450 in B6C3F1 mice. Exposure to either doxylamine or phenobarbital also resulted in decreases in serum thyroxine (T4) levels (approximately 80% of control) with compensatory increases in serum thyroid-stimulating hormone levels (approximately 4-fold). No clear changes in serum triiodothyronine levels were apparent. These findings are consistent with the hypothesis that doxylamine increases the activity of those hepatic enzymes involved in T4 metabolism.
Topics: Animals; Cytochrome P-450 Enzyme System; Doxylamine; Enzyme Induction; Female; Histamine H1 Antagonists; Hydroxylation; Lauric Acids; Male; Mice; Microsomes, Liver; Phenobarbital; Testosterone; Thyroid Hormones
PubMed: 8975784
DOI: 10.1006/taap.1996.0325 -
Journal of Pharmaceutical and... Oct 2022A simple, rapid, sensitive and specific LC-MS/MS method was developed and validated for the quantitative determination of doxylamine in human plasma, using isotope...
A simple, rapid, sensitive and specific LC-MS/MS method was developed and validated for the quantitative determination of doxylamine in human plasma, using isotope doxylamine-d5 as internal standard (IS). The detection was conducted on a QTRAP 5500 tandem mass spectrometer coupled with electrospray ionization (ESI) source in positive ion mode. Quantification was achieved by positive electrospray ionization containing multiple reaction monitoring (MRM) transitions of m/z 271.0→182.0 for doxylamine and m/z 276.2→187.3 for IS. The mobile phase A was methanol, and mobile phase B was 20 mM ammonium acetate (0.2 % formic acid) in water, using a gradient elution procedure at a flow rate of 0.6 mL/min. The method was validated with a sensitivity of 0.500 ng/mL and a linear concentration range of 0.500-200 ng/mL. The inter-batch precision (%CV) was less than 5.4 %, and the accuracy deviation (%RE) ranged from - 10.6 % to 3.7 %; the inter-batch precision (%CV) was less than 6.6 %, and the accuracy deviation (%RE) was ranged from - 2.7 % to 0.1 %. The selectivity, sensitivity, extraction recovery, matrix effect, carryover, dilution reliability, stability and other characteristics were within the acceptable range. This validated method was successfully applied to a bioequivalence study that orally administered 25 mg of doxylamine succinate tablets in 60 healthy Chinese volunteers.
Topics: Administration, Oral; China; Chromatography, Liquid; Doxylamine; Healthy Volunteers; Histamine H1 Antagonists; Humans; Methanol; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Tablets; Tandem Mass Spectrometry; Therapeutic Equivalency
PubMed: 35994945
DOI: 10.1016/j.jpba.2022.114984 -
The American Journal of the Medical... Jul 2001Doxylamine succinate, an over-the-counter antihistamine, is commonly used as a nighttime sleep aid in the short-term management of insomnia. It is also used in...
Doxylamine succinate, an over-the-counter antihistamine, is commonly used as a nighttime sleep aid in the short-term management of insomnia. It is also used in combination with antitussive and decongestant agents for the temporary relief of common cold symptoms. Doxylamine is frequently involved in accidental and intentional overdoses. Rhabdomyolysis and secondary acute renal failure are rare but potentially serious complications, making early recognition and treatment essential. With the large number of nonprescription antihistamines and sleep aids available to the general public, it is important to keep in mind that overdose is a potential problem. The complications associated with overdose of these medications are just as life threatening as those associated with prescription drugs. A high index of suspicion and evaluation of rhabdomyolysis is warranted in antihistamine toxicity. We report an observation of severe rhabdomyolysis associated with doxylamine overdose.
Topics: Acute Kidney Injury; Adult; Doxylamine; Drug Overdose; Histamine H1 Antagonists; Humans; Male; Nonprescription Drugs; Rhabdomyolysis; Self Medication
PubMed: 11465247
DOI: 10.1097/00000441-200107000-00009 -
Journal of AOAC International Dec 2022The combination of pyridoxine hydrochloride (PYR) and doxylamine succinate (DOX) as an antiemetic binary mixture is used to treat nausea and vomiting during pregnancy.
Chemometric Quality Assessment of Doxylamine Succinate With Its Degradation Product: Implementation of Two Predictive Models on UV-Spectrophotometric Data of Anti-Emetic Binary Mixture.
BACKGROUND
The combination of pyridoxine hydrochloride (PYR) and doxylamine succinate (DOX) as an antiemetic binary mixture is used to treat nausea and vomiting during pregnancy.
OBJECTIVE
Two validated, accurate, and selective chemometric models were developed to assay binary mixture in the presence of DOX oxidative degradation product (DOX DEG) that could be characterized using LC-MS.
METHODS
Partial least squares (PLS) regression and principal component regression (PCR) were selected for the determination of our binary mixture in presence of degradation. To exhibit a training set of 25 mixtures that had various percentages of tested substances in five level 3 variables, an experimental design was chosen. A set of 18 synthetic mixtures in the concentration range 10.0-50.0 μg/mL, 12.00-20.0 μg/mL, and 6.0-30.0 μg/mL for PYR, DOX, and DOX DEG, respectively, were used in the construction of the calibration models. Then set of seven synthetic mixtures with different concentrations were used in the construction of the validation models.
RESULTS
In validation samples with low root mean square error of prediction (RMSEP), the suggested models successfully predicted the concentrations of our drugs. The models developed were evaluated by RMSEP calculation, and the values obtained were 0.341, 0.196, and 0.388 for PYR, DOX, and DOX DEG, respectively, using PLS. While using PCR, RMSEP calculation and the values obtained were 0.400, 0.256, and 0.375 for PYR, DOX, and DOX DEG, respectively. The developed models were validated according to ICH strategies.
CONCLUSIONS
The corresponding methods are suitable to determine PYR and DOX in pure form, pharmaceutical dosage form, and in the presence of DOX DEG product.
HIGHLIGHTS
The study of drug breakdown pathways is very important nowadays, so even in the presence of degradation and extreme spectral overlapping, the suggested PLS and PCR spectrophotometric approaches were able to identify PYR and DOX.
Topics: Antiemetics; Chemometrics; Spectrophotometry; Doxylamine; Least-Squares Analysis; Calibration; Spectrophotometry, Ultraviolet
PubMed: 35904581
DOI: 10.1093/jaoacint/qsac090 -
Clinical Toxicology (Philadelphia, Pa.) Mar 2015Doxylamine is a first-generation antihistamine similar in structure to diphenhydramine. Unlike diphenhydramine, however, there is a paucity of data regarding the risk of... (Observational Study)
Observational Study
BACKGROUND
Doxylamine is a first-generation antihistamine similar in structure to diphenhydramine. Unlike diphenhydramine, however, there is a paucity of data regarding the risk of toxicity following unintentional exposures in pediatric patients.
METHODS
We performed an observational case series with data collected retrospectively from a poison system database for all single-substance pediatric (5 years-old and younger) doxylamine ingestions for the period of 1997-2012. Data collected included age, gender, weight, reason for exposure, exact or estimated maximum dose, clinical effects and medical interventions.
RESULTS
A total of 140 cases were identified; 74 (53%) involved males. Ages ranged 6 months to 5 years. In 30 cases (21%), the exact amount ingested was documented and ranged from 6.25-50 mg with a maximum weight-based dose of 6.2 mg/kg. In 76 cases, the estimated maximum dose ranged from 12.5 to 375 mg with a maximum weight-based dose of 37 mg/kg. All symptoms were mild and self-limiting. The only documented intervention was the administration of activated charcoal in 13 cases.
CONCLUSION
Unintentional isolated pediatric doxylamine ingestions did not result in significant toxicity in our 140 cases. Reported doses of up to 6.2 mg/kg resulted in only transient drowsiness and tachycardia.
Topics: Accidents; Age Factors; Antidotes; California; Charcoal; Child, Preschool; Dose-Response Relationship, Drug; Doxylamine; Female; Histamine H1 Antagonists; Humans; Infant; Male; Poisoning; Retrospective Studies; Risk Assessment; Risk Factors; Sleep Stages; Tachycardia; Treatment Outcome
PubMed: 25661472
DOI: 10.3109/15563650.2015.1006400 -
Journal of Clinical Epidemiology Dec 2022
Topics: Pregnancy; Female; Humans; Doxylamine; Antiemetics; Nausea
PubMed: 36223814
DOI: 10.1016/j.jclinepi.2022.10.007 -
Hospital Pharmacy Jul 2013Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The...
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, call The Formulary at 800-322-4349. The July 2013 monograph topics are prothrombin complex concentrate (human), cysteamine bitartrate delayed-release capsules, doxylamine succinate/pyridoxine hydrochloride, tedizolid phosphate, and sofosbuvir. The DUE/MUE is on canaglifozin.
PubMed: 24421524
DOI: 10.1310/hpj4807-580 -
The New England Journal of Medicine Mar 2014
Topics: Antiemetics; Congenital Abnormalities; Dicyclomine; Doxylamine; Drug Approval; Drug Combinations; Female; History, 20th Century; Humans; Morning Sickness; Pregnancy; Pyridoxine; United States; United States Food and Drug Administration
PubMed: 24645939
DOI: 10.1056/NEJMp1316042 -
JAMA
Topics: Abnormalities, Drug-Induced; Dicyclomine; Doxylamine; Drug Combinations; Drug Evaluation; Female; Humans; Maternal-Fetal Exchange; Pregnancy; Pyridines; Pyridoxine
PubMed: 7241787
DOI: No ID Found