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Biological & Pharmaceutical Bulletin 2019To date, limited drug information is available for the individual optimization of pharmacotherapy. The author attempted multiple evaluations of patient data on factors... (Review)
Review
To date, limited drug information is available for the individual optimization of pharmacotherapy. The author attempted multiple evaluations of patient data on factors related to the pharmacokinetics, drug efficacy, and adverse reactions observed in clinical settings. Through the clinical studies, drug information on the individual optimization of pharmacotherapy needed by health professionals including physicians and pharmacists was identified. Major findings were: 1) Cachectic cancer patients had high plasma concentrations of oxycodone via the reduction of CYP3A activity. The metabolic reduction in cachectic cancer patients was potentially related to the elevated serum level of interleukin-6. 2) Dopamine receptor D (DRD2) genetic mutations and being female led to poor antiemetic efficacy of the treatment of opioid-induced nausea in prochlorperazine-treated patients. The opioid receptor μ1 (OPRM1) wild genotype in addition to being female and having high plasma concentrations of prochlorperazine increased prolactin secretion during oxycodone treatment. 3) Rheumatoid arthritis patients with a genetic mutation of ATP-binding cassette subfamily B member 1 (ABCB1) had high plasma concentrations of tacrolimus and its 13-O-demethylate. The ABCB1 genetic mutation and associated high plasma concentration of tacrolimus decreased kidney function. 4) Chronic inflammation increased the plasma voriconazole concentration via its poor metabolism, whereas it did not alter the plasma itraconazole concentration. Although co-administration of prednisolone did not affect the plasma concentration of triazole antifungals, it weakly increased voriconazole metabolism. 5) In breastfeeding women, the median milk/plasma concentration ratio of amlodipine was 0.85. However, the observed relative infant dose of amlodipine in most patients was less than 10%.
Topics: Drug Therapy; Female; Humans; Male; Precision Medicine; Sex Factors
PubMed: 30713247
DOI: 10.1248/bpb.b18-00766 -
Cell Mar 2020Monoclonal antibodies (mAbs) targeting antigens expressed at the surface of tumor cells are widely used for cancer control in clinics, but these treatments need to be...
Monoclonal antibodies (mAbs) targeting antigens expressed at the surface of tumor cells are widely used for cancer control in clinics, but these treatments need to be improved. Chew et al. show how an old drug, prochlorperazine, could be repurposed to enhance the efficacy of anti-tumor mAbs by increasing the cell-surface expression of tumor antigens.
Topics: Antibodies, Monoclonal; Antibody-Dependent Cell Cytotoxicity; Antigens, Neoplasm; Endocytosis; Humans; Neoplasms
PubMed: 32142673
DOI: 10.1016/j.cell.2020.02.025 -
American Journal of Health-system... Jan 2018The stability of an extemporaneously prepared preservative-free prochlorperazine 5-mg/mL nasal spray was evaluated.
PURPOSE
The stability of an extemporaneously prepared preservative-free prochlorperazine 5-mg/mL nasal spray was evaluated.
METHODS
The preservative-free prochlorperazine nasal spray was prepared by adding 250 mg of prochlorperazine edisylate to 50 mL of citrate buffer in a low-density polyethylene nasal spray bottle. A stability-indicating high-performance liquid chromatography (HPLC) method was developed and validated using the major degradant prochlorperazine sulfoxide and by performing forced-degradation studies. For chemical stability studies, 3 100-μL samples of the preservative-free prochlorperazine from 5 nasal spray bottles stored at room temperature were collected at days 0, 20, 30, 45, and 60 and were assayed in triplicate using the stability-indicating HPLC method. Microbiological testing involved antimicrobial effectiveness testing based on () chapter 51 and quantitative microbiological enumeration of aerobic bacteria, yeasts, and mold based on chapter 61. Samples for microbiological testing were collected at days 0, 30, and 60.
RESULTS
The stability-indicating HPLC method clearly identified the degradation product prochlorperazine sulfoxide without interference from prochlorperazine. All tested solutions retained over 90% of the initial prochlorperazine concentration for the 60-day study period. There were no detectable changes in color, pH, and viscosity in any sample. There was no growth of bacteria, yeast, and mold for 60 days in all samples tested.
CONCLUSION
An extemporaneously prepared preservative-free nasal spray solution of prochlorperazine edisylate 5 mg/mL was physically, chemically, and microbiologically stable for 60 days when stored at room temperature in low-density polyethylene bottles.
Topics: Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Dopamine Antagonists; Drug Compounding; Drug Stability; Drug Storage; Nasal Sprays; Prochlorperazine; Time Factors
PubMed: 29273610
DOI: 10.2146/ajhp160531 -
Acta Neurologica Taiwanica Jun 2017In 2015, the American Headache Society (AHS) amended the treatment guideline of acute migraine based on evidence-based medicine (EBM) that all triptans in any form of...
In 2015, the American Headache Society (AHS) amended the treatment guideline of acute migraine based on evidence-based medicine (EBM) that all triptans in any form of preparations, acetaminophen, and non-steroid anti-inflammation drugs-NSAID (aspirin, diclofenac, ibuprofen, naproxen), sumatriptan/naproxen, combined acetaminophen/aspirin/caffeine are considered effective (Level A). Previously effective drugs as prochlorperazine, and dihydroergotamine-DHE (excluded inhaled form) were downrated to probable effective (Level B). Taiwan Headache Society published its treatment guideline for acute migraine attack in 2007. It should be updated based on the new available evidence. The Treatment Guideline Subcommittee of Taiwan Headache Society reviewed the recent trials, evaluated the grade of evidence, and appraised the clinical efficacy to reach a new consensus. We also referred to the guidelines from United States, Europe, Canada and other countries to make this one meets our needs and feasible. Acute medications currently available in Taiwan can be categorized into "migraine-specific"and"migraine-nonspecific" groups. Migraine-specific triptans and migraine-nonspecific nonsteroidal antiinflammatory drugs (NSAIDs) have the best levels of evidence, and are recommended as the first-line medications for acute migraine attacks. The administration should follow the concept of "stratified care". For mild to moderate migraine attacks, oral NSAIDs are the first choice; with oral aspirin, combination analgesics, intravenous/intramuscular NSAIDs as alternatives. For moderate to severe attacks, oral or nasal spray triptans and ergotamine/caffeine compounds are recommended and should be administered in the early stage of migraine attacks. Antiemetics can be used as supplement to alleviate nausea and vomiting. Notably, a combination of a triptan and a NSAID yielded a better efficacy compared with either therapy alone. Parenteral steroid and fluid supply are the first choice in treatment of status migrainosus. Acetaminophen is suitable for mild to moderate migraine attacks and remains the first choice for children and pregnant women. Opiates are not recommended for acute migraine treatment at the present time because of serious adverse events. To prevent medication-overuse headache, the use of acute treatment should be limited to a maximum of ten days a month.
Topics: Acute Disease; Anti-Inflammatory Agents, Non-Steroidal; Humans; Migraine Disorders; Practice Guidelines as Topic; Tryptamines
PubMed: 29250761
DOI: No ID Found -
Indian Journal of Otolaryngology and... Dec 2023To assess the efficacy and safety of prochlorperazine in Indian patients with acute vertigo.
AIM
To assess the efficacy and safety of prochlorperazine in Indian patients with acute vertigo.
METHODS
In this prospective, multicenter, open-label, post-marketing observational study, patients with acute peripheral vertigo of different etiologies received 5 mg prochlorperazine thrice a day for 5 days. The primary endpoints were percentage of patients with improvement in (1) vertigo symptoms and (2) clinical response as per scale for vestibular vertigo severity level and clinical response evaluation (SVVSLCRE) from baseline to end of treatment (Day 6). The key secondary endpoints were (1) improvement in nystagmus grading, and (2) safety and tolerability Efficacy of prochlorperazine by route of administration of first prochlorperazine dose (oral or intramuscular) was also assessed.
RESULTS
Of 1716 enrolled patients (mean [standard deviation, SD]) age (42.0 [12.95] years; 53.6% men), 57.4% were diagnosed with Meniere's disease, followed by vestibular neuritis (17.4%), labyrinthitis (16.7%), or ear surgery (8.5%). In the overall population, 91.1% of patients showed improvement in clinical response per SVVSLCRE grading at Day 6 (p < 0.0001 vs. non-responders). Nystagmus grading was improved in 99.7% (of patients. No adverse drug reactions events were reported. Tolerability of prochlorperazine was rated as good, very good, and excellent by 43.6%, 32.9% and 20.7% of patients, respectively. Among patients with postoperative vertigo, 80.1% showed improvement in clinical response. In the intramuscular and oral subsets, 85.5% and 92.1% of patients showed improved clinical response, respectively.
CONCLUSION
Prochlorperazine showed improvement in severity of symptoms and clinical response in all subsets of vertigo patients, with a good safety and tolerability profile.
TRIAL REGISTRATION NUMBER
CTRI/2022/01/039287.
DATE OF REGISTRATION
10 January 2022.
PubMed: 38027535
DOI: 10.1007/s12070-023-03831-0 -
Pediatric Neurology Mar 2021A combination of parenteral medications (often referred to as standard combination therapy) is frequently used in the treatment of acute migraine in the pediatric... (Observational Study)
Observational Study
BACKGROUND
A combination of parenteral medications (often referred to as standard combination therapy) is frequently used in the treatment of acute migraine in the pediatric emergency department (PED). The primary aim of this study was to evaluate the two-hour, 24-hour, and seven-day impact of one such regimen on pain in children who present to the PED. Standard combination therapy for purposes of our study is defined as a bolus of intravenous saline, and a combination of intravenous ketorolac, prochlorperazine, and diphenhydramine.
METHODS
This prospective observational study included 120 children between the ages seven and 18 years who presented to the PED with migraine, whose parents could read and understand the consent form in English, and who were treated with standard combination therapy. The primary outcome measure for this study was the change in severity of pain as noted by the child using the Faces Pain Scale-Revised. We analyzed normally distributed continuous variables by mean and standard deviation, whereas non-normally distributed continuous variables are reported by median and interquartile range.
RESULTS
Nonparametric Friedman testing on the entire cohort (n = 120) noted that there was a statistically significant change in the Faces pain scale from before administration of standard combination therapy to the two-hour, 24-hour, and one-week time point with a reduction in pain score of 87.5%, 100%, and 50%, respectively, at the three time points.
CONCLUSIONS
This study noted moderate relief of pain after administration of standard combination therapy, which persisted at one-week after administration.
Topics: Acute Disease; Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Child; Diphenhydramine; Dopamine Antagonists; Drug Therapy, Combination; Female; Humans; Hypnotics and Sedatives; Ketorolac; Male; Migraine Disorders; Outcome Assessment, Health Care; Prochlorperazine; Prospective Studies; Saline Solution
PubMed: 33493999
DOI: 10.1016/j.pediatrneurol.2020.12.004 -
AAPS PharmSciTech Jun 2022Sumatriptan succinate and prochlorperazine maleate are a clinically proven combination for treating migraine and associated nausea and vomiting. Classical oral dosage...
Sumatriptan succinate and prochlorperazine maleate are a clinically proven combination for treating migraine and associated nausea and vomiting. Classical oral dosage forms are not frequently workable in migraine because of the associated nausea/vomiting, and no effective fixed dose combination is available. Thus, the aim of the study was to optimize a combined sumatriptan-prochlorperazine orodispersible film for rapid release of drugs. Orodispersible films were prepared by solvent casting method using varied amounts of polyvinyl alcohol and glycerol as film former and plasticizer, respectively, along with fixed levels of other ingredients employing central composite design. The optimum film (VF) demonstrated disintegration and total dispersion times as 21 s and 2.3 min, respectively. Tensile strength and Young's modulus were 8.86 ± 0.37 MPa and 24.15 ± 0.07 MPa, respectively. The in vitro T80% of both drugs from the ODF was achieved within 4 min. The film was palatable and disintegrated in 2 min in buccal cavity of human volunteers. Permeation study through goat mucosa demonstrated 100% permeation of both drugs within 15 min. X-Ray diffraction and differential scanning calorimetry supported drugs being amorphous and Fourier transform infrared demonstrated drug-excipient compatibility in optimized film. A judicious combination of sumatriptan succinate and prochlorperazine maleate could be prepared in orodispersible films for the possible relief of migraine.
Topics: Excipients; Humans; Migraine Disorders; Nausea; Prochlorperazine; Sumatriptan; Vomiting
PubMed: 35655105
DOI: 10.1208/s12249-022-02307-8 -
Journal of Intensive Care Medicine Oct 2022Ondansetron is a preferred anti-emetic in critical care to treat nausea and vomiting, and has historically been considered a largely safe option. A recent...
Ondansetron is a preferred anti-emetic in critical care to treat nausea and vomiting, and has historically been considered a largely safe option. A recent pharmacoepidemiology study reported that ondansetron may be associated with an increased risk for acute kidney injury (AKI). We interrogated the High-Density Intensive Care (HiDenIC-15) database containing intensive care data for 13 hospitals across Western Pennsylvania between Oct 2008-Dec 2014. AKI was defined using the Kidney Disease, Improving Global Outcomes 2012 guidelines. Ondansetron use was considered as receiving any form of ondansetron within 24 h of admission. The subsequent 48 h (hours 25-72 after admission) were analyzed for outcomes. Primary outcome was development of AKI; secondary outcomes included 90-day mortality and time to AKI. Propensity-matched, multivariate logistic regression was applied for both outcomes. Comparator groups were metoclopramide and prochlorperazine using the same exposure criteria. AKI occurred in 965 (5.6%), 12 (3.0%), and 61 (6.5%) patients receiving ondansetron, prochlorperazine, and metoclopramide, respectively. In the adjusted analysis, no anti-emetic was associated with a significant change in the odds of developing AKI. Ondansetron was associated with a 5.48% decrease (CI -6.17--4.79) in death within 90 days of ICU-admission, which was independent of AKI status; an effect not seen with other anti-emetics. Anti-emetic usage was not associated with a change in the time to first AKI. Anti-emetic usage did not alter AKI risk. Ondansetron was associated with a significant decrease in 90-day mortality that was not seen by other anti-emetics, which requires further exploration.
Topics: Acute Kidney Injury; Antiemetics; Critical Illness; Humans; Intensive Care Units; Kidney; Metoclopramide; Ondansetron; Prochlorperazine
PubMed: 35000482
DOI: 10.1177/08850666211073582 -
Daru : Journal of Faculty of Pharmacy,... Sep 2018Fluphenazine and prochlorperazine as phenothiazine-class antipsychotic drugs are widely used to treat schizophrenia, however their use is associated with significant...
PURPOSE
Fluphenazine and prochlorperazine as phenothiazine-class antipsychotic drugs are widely used to treat schizophrenia, however their use is associated with significant side effects such as extrapyramidal symptoms, as well as ocular and skin disorders. Our goal was to determine the effect of fluphenazine and prochlorperazine on cell viability and melanogenesis in lightly pigmented normal human melanocytes.
METHODS
The viability of melanocytes was evaluated by the WST-1 colorimetric assay, while melanin content and tyrosinase activity were tested spectrophotometrically.
RESULTS
It has been shown that both phenothiazines induce the concentration-dependent loss in cell viability. The EC values were calculated to be 6.13 and 0.63 μM for fluphenazine and prochlorperazine, respectively. Fluphenazine in the concentration of 5.0 μM and prochlorperazine in concentrations of 0.5 and 0.75 μM decreased melanin content and tyrosinase activity. The observed inhibition of melanogenesis may be explained by the decrease of enzyme activity.
CONCLUSIONS
The demonstrated changes in melanization process in lightly pigmented cells exposed to fluphenazine and prochlorperazine in vitro suggest a significant role of melanin and melanocytes in the mechanisms of undesirable side effects of these drugs in vivo. Graphical abstract Fluphenazine and prochlorperazine significantly inhibits melanogenesis in lightly pigmented melanocytes HEMn-LP.
Topics: Cell Survival; Cells, Cultured; Fluphenazine; Humans; Melanins; Melanocytes; Monophenol Monooxygenase; Prochlorperazine
PubMed: 30159761
DOI: 10.1007/s40199-018-0206-4 -
Headache Jun 2016To provide evidence-based treatment recommendations for adults with acute migraine who require treatment with injectable medication in an emergency department (ED). We... (Review)
Review
OBJECTIVE
To provide evidence-based treatment recommendations for adults with acute migraine who require treatment with injectable medication in an emergency department (ED). We addressed two clinically relevant questions: (1) Which injectable medications should be considered first-line treatment for adults who present to an ED with acute migraine? (2) Do parenteral corticosteroids prevent recurrence of migraine in adults discharged from an ED?
METHODS
The American Headache Society convened an expert panel of authors who defined a search strategy and then performed a search of Medline, Embase, the Cochrane database and clinical trial registries from inception through 2015. Identified articles were rated using the American Academy of Neurology's risk of bias tool. For each medication, the expert panel determined likelihood of efficacy. Recommendations were created accounting for efficacy, adverse events, availability of alternate therapies, and principles of medication action.
RESULTS/CONCLUSIONS
The search identified 68 unique randomized controlled trials utilizing 28 injectable medications. Of these, 19 were rated class 1 (low risk of bias), 21 were rated class 2 (higher risk of bias), and 28 were rated class 3 (highest risk of bias). Metoclopramide, prochlorperazine, and sumatriptan each had multiple class 1 studies supporting acute efficacy, as did dexamethasone for prevention of headache recurrence. All other medications had lower levels of evidence.
RECOMMENDATIONS
Intravenous metoclopramide and prochlorperazine, and subcutaneous sumatriptan should be offered to eligible adults who present to an ED with acute migraine (Should offer-Level B). Dexamethasone should be offered to these patients to prevent recurrence of headache (Should offer-Level B). Because of lack of evidence demonstrating efficacy and concern about sub-acute or long-term sequelae, injectable morphine and hydromorphone are best avoided as first-line therapy (May avoid-Level C).
Topics: Adult; Databases, Bibliographic; Disease Management; Emergency Service, Hospital; Humans; Injections, Intraperitoneal; Migraine Disorders; Societies, Medical
PubMed: 27300483
DOI: 10.1111/head.12835