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Inflammation Research : Official... Apr 2006
Comparative Study
Topics: Benzothiepins; Diphenhydramine; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; In Vitro Techniques; Loratadine; Male; Platelet Activation; Platelet Aggregation
PubMed: 16547813
DOI: 10.1007/s00011-005-0038-9 -
Clinical Toxicology (Philadelphia, Pa.) Feb 2020Diphenhydramine (DPH) exposures in children may be the result of accidental unsupervised ingestions, caregiver error, and intentional misuse of DPH-containing cough and...
Diphenhydramine (DPH) exposures in children may be the result of accidental unsupervised ingestions, caregiver error, and intentional misuse of DPH-containing cough and cold medications (CCM). We sought to understand the nature of pediatric ingestions of DPH, particularly the toxicity and outcome of a single product, single ingredient DPH (DPH-only) exposures, in order to derive ingredient-specific information about the clinical effects and course of such cases. As part of a U.S. multi-year safety surveillance program to assess the safety of over-the-counter (OTC) medications used in cough and cold preparations in children <12 years of age, an expert panel reviewed cases involving symptomatic adverse events potentially related to oral exposures to these medications. After individual review, the cases were categorized by causal relationship of the reported ingredients to the adverse event, exposure intent (therapeutic, non-therapeutic, unknown intent), and dose (therapeutic, supratherapeutic, or unknown). Following panel review, any disagreement on classification was discussed until a consensus was reached. The data were then analyzed with respect to descriptive findings. The panel reviewed 6618 eligible cases and determined 2802 were at least potentially related to oral exposure to DPH. Of these, 2028 were DPH-only cases (39.1% of all cases judged at least potentially related to a cough and cold medication). The majority (79.5%) of DPH-only cases occurred in children 2 to <4 years of age and involved accidental unsupervised ingestions (74.7%). Liquid pediatric formulations were the most common (51.7%) products reported followed by solid pediatric formulations (24.0%). The most common adverse events were tachycardia (53.4%), hallucinations (46.5%), somnolence (34.7%), agitation (33.9%), and mydriasis (26.3%). Seizures occurred in only 5.5% of cases. Five (0.2%) deaths were reported; in the death cases, the DPH dose was judged supratherapeutic in one and unknown in the other four. Child abuse was reported in four of the five death cases and three of the five deaths were homicides. Exposures to DPH-only products were the most common type of exposure detected in our study of adverse events associated with CCM in children. The majority of the DPH-only cases were the result of accidental unsupervised ingestions. Most adverse events were relatively mild self-limited anticholinergic effects and few deaths occurred. Deaths involving DPH were often associated with child abuse or homicide. Interventions targeting the prevention of accidental unsupervised are likely to be impactful in preventing morbidity associated with DPH-only exposure.
Topics: Adverse Drug Reaction Reporting Systems; Antitussive Agents; Child; Cough; Diphenhydramine; Humans; Nonprescription Drugs
PubMed: 31062642
DOI: 10.1080/15563650.2019.1609683 -
Clinical Pharmacology in Drug... May 2018Diphenhydramine pharmacokinetics were characterized following a single oral dose in children aged 2 to 17 years using a weight- and age-based dosing schedule with more...
Diphenhydramine pharmacokinetics were characterized following a single oral dose in children aged 2 to 17 years using a weight- and age-based dosing schedule with more tiers than the current age-based dosing schedule recommended by the nonprescription drug monograph. This study was conducted in 42 subjects, aged 2 to 17 years. Doses were based on a weight-age dosing schedule, ranging from 6.25 to 50 mg. An oral dose was administered with water about 2 hours after a light breakfast. Plasma samples were obtained up to 48 hours after dosing and analyzed for diphenhydramine. Pharmacokinetic parameters were estimated using noncompartmental methods, and the relationship of oral clearance with age was assessed using linear regression. Over an 8-fold range of doses, C and AUC increased ∼90 % to ∼140% across age groups, with a similar T (1.5 hours). Oral CL/F increased with age, but after allometric scaling, no maturation-related change in CL/F was apparent. Mild somnolence was the most commonly reported adverse event (95% of the subjects). A weight-age dosing schedule using an 8-fold range of doses achieved C and AUC that increased about 2-fold across age groups. No effect of maturation on CL/F was observed after allometric scaling.
Topics: Administration, Oral; Adolescent; Area Under Curve; Body Weight; Child; Child, Preschool; Diphenhydramine; Drug Dosage Calculations; Female; Half-Life; Humans; Male; Metabolic Clearance Rate
PubMed: 28967696
DOI: 10.1002/cpdd.391 -
Forensic Toxicology Jan 2023Diphenhydramine is an antihistamine drug widely used to alleviate symptoms caused by allergies and the common cold. Diphenhydramine-involved fatalities have been...
PURPOSE
Diphenhydramine is an antihistamine drug widely used to alleviate symptoms caused by allergies and the common cold. Diphenhydramine-involved fatalities have been reported in the past but usually involving overdose by ingestion. We report a peculiar case of fatal hypothermia during non-winter season involving topical diphenhydramine.
METHODS
A 23-year-old male with no known preexisting medical conditions was found dead in the bathroom of his apartment with a small amount of running water on his back. Postmortem examinations and toxicological analysis on blood and urine were performed.
RESULTS
Color difference was apparent between the right and left cardiac blood. Wischnewski spots were observed in the gastric mucosa. Histological examination revealed no obvious findings that could attribute to serious cardiovascular events. Drug screening by gas chromatograph-tandem mass spectrometry (GC/MS/MS) detected diphenhydramine in blood and urine. Further quantification revealed the postmortem concentrations to be 0.44 μg/mL in blood and 2500 μg/mL in urine.
CONCLUSIONS
The cause of death was determined to be hypothermia. Diphenhydramine-induced drowsiness and possible intrinsic cardiac factor may have led to prolonged impaired consciousness, preventing his ability to escape from the running cold water leading to hypothermia and death.
Topics: Male; Humans; Young Adult; Adult; Diphenhydramine; Hypothermia; Tandem Mass Spectrometry; Gas Chromatography-Mass Spectrometry; Water
PubMed: 36652061
DOI: 10.1007/s11419-022-00637-7 -
Journal of the American Geriatrics... Jun 1959
Topics: Aged; Diphenhydramine; Humans; Orphenadrine; Parkinson Disease
PubMed: 13653948
DOI: 10.1111/j.1532-5415.1959.tb00178.x -
Journal of Pharmaceutical Sciences Dec 1973
Topics: Aldehydes; Diphenhydramine; Ethanol; Hydrolysis; Methanol; Methods; Solutions; Spectrophotometry, Ultraviolet; Temperature
PubMed: 4762171
DOI: 10.1002/jps.2600621220 -
The Journal of Biological Chemistry May 1949
Topics: Diphenhydramine
PubMed: 18119258
DOI: No ID Found -
Biochemical Pharmacology Nov 1994The metabolism of praziquantel (PZQ) was studied in microsomes isolated from livers of differently pretreated rats and in the presence of various inhibitors of...
The metabolism of praziquantel (PZQ) was studied in microsomes isolated from livers of differently pretreated rats and in the presence of various inhibitors of cytochrome P450 (P450) isoforms. Microsomes from phenobarbitone (PB)-pretreated rats metabolised PZQ to its major metabolite 4OH-praziquantel (4OH-PZQ) at a greater rate than those from 20-methylcholanthrene (MC) and saline (SA) pretreated rats. The Vmax for the PB microsomes was 600 nmol 4OH-PZQ formed/mg/min x 10(-3) compared to 91.4 nmol/mg/min x 10(-3) for MC and 238 nmol/mg/min x 10(-3) for SA microsomes. These results indicate that PZQ is metabolised by PB-inducible isoforms of P450. Inhibitor studies were conducted with microsomes from SA-pretreated animals. In these studies, caffeine, disulfuram, and tolbutamide were poor inhibitors of the metabolism of PZQ to 4OH-PZQ, with I50 values not determinable. Quinidine and quinine inhibited the hydroxylation of PZQ but with high Ki values. 17 alpha-Ethynylestradiol, cimetidine and diphenylhydramine were effective inhibitors of the formation of 4OH-PZQ, with 17 alpha-ethynylestradiol being the most potent with a Ki of 0.5 +/- 0.05 microM. From the known specificities of these P450 inhibitors, it is therefore concluded that cytochromes P450 1A2, 2E1, 2C9-10, and 2D6 probably do not contribute significantly to the metabolism of PZQ to its major metabolite in rats. It is likely that cytochromes P450 2B1 and 3A, both inducible by PB, are predominantly responsible for the formation of 4OH-PZQ.
Topics: Animals; Cytochrome P-450 Enzyme Inhibitors; Diphenhydramine; Hydroxylation; Kinetics; Male; Microsomes, Liver; Praziquantel; Quinidine; Quinine; Rats; Rats, Sprague-Dawley
PubMed: 7980647
DOI: 10.1016/0006-2952(94)90464-2 -
Clinical Pharmacology and Therapeutics Apr 1984Diphenhydramine (DPHM) disposition was examined in nine patients with chronic alcohol-related liver disease and in eight normal subjects. Sleep of 1 to 2 hr duration was...
Diphenhydramine (DPHM) disposition was examined in nine patients with chronic alcohol-related liver disease and in eight normal subjects. Sleep of 1 to 2 hr duration was induced in all subjects by a 0.8 mg/kg iv dose without an apparent increase in cerebral sensitivity in the patients with cirrhosis. Protein binding as determined by equilibrium dialysis (3H-DPHM) revealed a 15% decrease in the cirrhotic patients, while recovery of unchanged DPHM in urine (2%) was of the same order in the two groups. Computerized biexponential curve analysis was used to compare the plasma profiles for five of the patients and six of the normal subjects. Monoexponential curve analysis of the terminal beta-phase, including all subjects, was also used to compare the two groups. The means of plasma clearance and apparent volume of distribution in cirrhotic patients were respectively less and greater than in normal subjects, but these differences were not significant. The t1/2 for the beta-phase (t1/2 beta), which reflects this reciprocal trend, was increased in the patients (15.2 +/- 1.5 and 9.3 +/- 0.9 hr). This correlated in part with severity of disease, with r = 0.723 between t1/2 beta and the serum bilirubin levels. In conclusion, a single intravenous dose of DPHM provided safe and effective sedation in patients with cirrhosis.
Topics: Adult; Blood Proteins; Diphenhydramine; Humans; Injections, Intravenous; Kinetics; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Protein Binding
PubMed: 6705445
DOI: 10.1038/clpt.1984.63 -
Science (New York, N.Y.) Apr 2016Pharmaceutical manufacturing typically uses batch processing at multiple locations. Disadvantages of this approach include long production times and the potential for...
Pharmaceutical manufacturing typically uses batch processing at multiple locations. Disadvantages of this approach include long production times and the potential for supply chain disruptions. As a preliminary demonstration of an alternative approach, we report here the continuous-flow synthesis and formulation of active pharmaceutical ingredients in a compact, reconfigurable manufacturing platform. Continuous end-to-end synthesis in the refrigerator-sized [1.0 meter (width) × 0.7 meter (length) × 1.8 meter (height)] system produces sufficient quantities per day to supply hundreds to thousands of oral or topical liquid doses of diphenhydramine hydrochloride, lidocaine hydrochloride, diazepam, and fluoxetine hydrochloride that meet U.S. Pharmacopeia standards. Underlying this flexible plug-and-play approach are substantial enabling advances in continuous-flow synthesis, complex multistep sequence telescoping, reaction engineering equipment, and real-time formulation.
Topics: Chemistry, Pharmaceutical; Diazepam; Diphenhydramine; Lidocaine; Pharmaceutical Preparations; Pharmacopoeias as Topic
PubMed: 27034366
DOI: 10.1126/science.aaf1337