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Gynecological Endocrinology : the... Dec 2023In recent years, new combined oral contraceptives (COCs) have become available, representing an advance in terms of individualization and compliance by users. To... (Review)
Review
In recent years, new combined oral contraceptives (COCs) have become available, representing an advance in terms of individualization and compliance by users. To provide recommendations regarding COCs: formulations, use, efficacy, benefits and safety. For these recommendations, we have used the modified Delphi methodology and carried out a systematic review of studies found in the literature and reviews performed in humans, published in English and Spanish in Pubmed, Medline and advanced medicine and computer networks until the year 2021, using the combination of terms: 'oral contraceptives', 'estroprogestins' and 'combined oral contraceptives'. Regarding the estrogen component, initially switching from mestranol (the pro-drug of ethinylestradiol) to ethinylestradiol (EE) and then reducing the EE dose helped reduce side effects and associated adverse events. Natural estradiol and estradiol valerate are already available and represent a valid alternative to EE. The use of more potent 19-nortestosterone-derived progestins, in order to lower the dose and then the appearance of non-androgenic progestins with different endocrine and metabolic characteristics, has made it possible to individualize the prescription of COC according to the profile of each woman. Advances in the provision of new COCs have improved the risk/benefit ratio by increasing benefits and reducing risks. Currently, the challenge is to tailor contraceptives to individual needs in terms of safety, efficacy, and protection of female reproductive health.
Topics: Female; Humans; Contraceptives, Oral, Combined; Progestins; Latin America; Ethinyl Estradiol; Estrogens; Women's Health
PubMed: 37857350
DOI: 10.1080/09513590.2023.2271072 -
Medical Science Monitor : International... Jun 2014Pain on injection is an acknowledged adverse effect (AE) of propofol administration for the induction of general anesthesia. Flurbiprofen axetil has been reported to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pain on injection is an acknowledged adverse effect (AE) of propofol administration for the induction of general anesthesia. Flurbiprofen axetil has been reported to reduce the pain of injection. However, results of published papers on the efficacy of flurbiprofen axetil in managing pain on injection of propofol are inconsistent.
MATERIAL/METHODS
We conducted a comprehensive meta-analysis of studies to appraise the efficacy and safety of flurbiprofen axetil for controlling pain induced by propofol injection. The pooled risk ratio (RR) with corresponding 95% confidence intervals (CI) was calculated employing fixed- or random-effects models, depending upon the heterogeneity of the included trials.
RESULTS
Compared with the placebo group, flurbiprofen axetil allows more patients to have no pain (RR 3.51, 95% CI 2.22-5.55, p=0.000), and decreases the cumulative number of patients with mild, moderate, and severe pain on injecting propofol (RR 0.70, 95% CI 0.58-0.86, p=0.000; RR 0.59, 95% CI 0.46-0.75, p=0.000; RR 0.25, 95% CI 0.16-0.38, p=0.000, respectively). In the stratified analysis by the doses, flurbiprofen axetil at a dose of over 50 mg was found to be effective in reducing propofol-induced pain on injection; however, there were no significant differences in relieving pain between treatment and placebo groups with flurbiprofen axetil at a dose of 25 mg. In terms of drug safety, there were no adverse effects (AEs) reported between flurbiprofen axetil-based regimens and placebo regimens.
CONCLUSIONS
Flurbiprofen axetil, an injectable prodrug of flurbiprofen, can significantly prevent or relieve the pain induced by propofol injection. More studies are required to assess its adverse effects.
Topics: Clinical Trials as Topic; Flurbiprofen; Humans; Pain; Propofol; Publication Bias; Risk Factors; Treatment Outcome
PubMed: 24935068
DOI: 10.12659/MSM.890102 -
Healthcare (Basel, Switzerland) Jun 2022Postherpetic neuralgia (PHN) is a common, painful, and long-term complication of herpes zoster (HZ). PHN increases the demand for healthcare services and, previous... (Review)
Review
Postherpetic neuralgia (PHN) is a common, painful, and long-term complication of herpes zoster (HZ). PHN increases the demand for healthcare services and, previous studies showed that patients who received antiviral agents were less likely to develop PHN. The objective of this study was to compare the efficacy of prodrugs and acyclovir in treating PHN among patients with HZ. The search included the PubMed, Medline, Embase, and Cochrane Center of Register of Controlled Trails databases through February 2022. Clinical trials and randomized controlled trials (RCTs) involving antiviral agent intervention for HZ patients diagnosed with PHN were eligible for inclusion. A meta-analysis was conducted to calculate pooled risk ratios (RRs) with 95% confidence intervals (CIs) with a fix-effect model. Five RCTs with 1147 HZ patients met our eligibility criteria. Our meta-analysis found that there was a significantly lower risk of PHN for members of the prodrugs group (famciclovir and valaciclovir) compared with those who received acyclovir (RR = 0.86, 95%, CI: 0.75 to 0.98, = 0.03). The review of studies indicated that the efficacy of prodrugs was better than acyclovir for reliving PHN.
PubMed: 35885708
DOI: 10.3390/healthcare10071181 -
Journal of Cardiothoracic and Vascular... Oct 2019Reducing mortality is a key target in critical care and perioperative medicine. The authors aimed to identify all nonsurgical interventions (drugs, techniques,...
OBJECTIVE
Reducing mortality is a key target in critical care and perioperative medicine. The authors aimed to identify all nonsurgical interventions (drugs, techniques, strategies) shown by randomized trials to increase mortality in these clinical settings.
DESIGN
A systematic review of the literature followed by a consensus-based voting process.
SETTING
A web-based international consensus conference.
PARTICIPANTS
Two hundred fifty-one physicians from 46 countries.
INTERVENTIONS
The authors performed a systematic literature search and identified all randomized controlled trials (RCTs) showing a significant increase in unadjusted landmark mortality among surgical or critically ill patients. The authors reviewed such studies during a meeting by a core group of experts. Studies selected after such review advanced to web-based voting by clinicians in relation to agreement, clinical practice, and willingness to include each intervention in international guidelines.
MEASUREMENTS AND MAIN RESULTS
The authors selected 12 RCTs dealing with 12 interventions increasing mortality: diaspirin-crosslinked hemoglobin (92% of agreement among web voters), overfeeding, nitric oxide synthase inhibitor in septic shock, human growth hormone, thyroxin in acute kidney injury, intravenous salbutamol in acute respiratory distress syndrome, plasma-derived protein C concentrate, aprotinin in high-risk cardiac surgery, cysteine prodrug, hypothermia in meningitis, methylprednisolone in traumatic brain injury, and albumin in traumatic brain injury (72% of agreement). Overall, a high consistency (ranging from 80% to 90%) between agreement and clinical practice was observed.
CONCLUSION
The authors identified 12 clinical interventions showing increased mortality supported by randomized controlled trials with nonconflicting evidence, and wide agreement upon clinicians on a global scale.
Topics: Cardiac Surgical Procedures; Critical Care; Critical Illness; Humans; Internet; Mortality; Perioperative Care; Physicians; Randomized Controlled Trials as Topic; Surveys and Questionnaires
PubMed: 31064730
DOI: 10.1053/j.jvca.2019.03.022 -
European Journal of Medicinal Chemistry Dec 2022Platinum-based antitumor drugs have been used in many types of tumors due to its broad antitumor spectrum in clinic. Encouraged by the cisplatin's (CDDP) worldwide... (Review)
Review
Platinum-based antitumor drugs have been used in many types of tumors due to its broad antitumor spectrum in clinic. Encouraged by the cisplatin's (CDDP) worldwide success in cancer chemotherapy, the research in platinum-based antitumor drugs has evolved from traditional platinum drug to multi-ligand and multifunctional platinum prodrugs over half a century. With the rapid development of metal drugs and the anticancer immune response, challenges and opportunities in platinum drug research have been shifted from traditional platinum-based drugs to platinum-based hybrids and the direction of development is tending toward photodynamic therapy, nano-delivery therapy, drug combination, targeted therapy, diagnostic therapy, immune-combination therapy and tumor stem cell therapy. In this review, we first exhaustively overviewed the role of platinum-based antitumor prodrugs and the anticancer immune response in medicinal inorganic chemistry based on the special nanomaterials, the modification of specific ligands, and the multiple functions obtained that are beneficial for tumor therapy in the last five years. We also categorized them according to drug potency and function. There hasn't been a comprehensive evaluation of precursor platinum drugs in prior articles. And a multifarious approach to distinguish and detail the variety of alterations of platinum-based precursors in various valence states also hasn't been summarized. In addition, this review points out the main problems at the interface of chemistry, biology, and medicine from their action mechanisms for current platinum drug development, and provides up-to-date potential strategies from drug design perspectives to circumvent those drawbacks. And a promising idea is also enlightened for researchers in the development and discovery of platinum prodrugs.
Topics: Humans; Platinum; Prodrugs; Antineoplastic Agents; Neoplasms; Chemistry, Inorganic; Ligands; Immunity
PubMed: 36152386
DOI: 10.1016/j.ejmech.2022.114680 -
Clinical Pharmacokinetics Oct 2019Enzyme-mediated biotransformation of pharmacological agents is a crucial step in xenobiotic detoxification and drug disposition. Herein, we investigated the metabolism...
Physicochemical Properties, Biotransformation, and Transport Pathways of Established and Newly Approved Medications: A Systematic Review of the Top 200 Most Prescribed Drugs vs. the FDA-Approved Drugs Between 2005 and 2016.
BACKGROUND
Enzyme-mediated biotransformation of pharmacological agents is a crucial step in xenobiotic detoxification and drug disposition. Herein, we investigated the metabolism and physicochemical properties of the top 200 most prescribed drugs (established) as well as drugs approved by the US Food and Drug Administration (FDA) between 2005 and 2016 (newly approved).
OBJECTIVE
Our objective was to capture the changing trends in the routes of administration, physicochemical properties, and prodrug medications, as well as the contributions of drug-metabolizing enzymes and transporters to drug clearance.
METHODS
The University of Washington Drug Interaction Database (DIDB) as well as other online resources (e.g., CenterWatch.com, Drugs.com, DrugBank.ca, and PubChem.ncbi.nlm.nih.gov) was used to collect and stratify the dataset required for exploring the above-mentioned trends.
RESULTS
Analyses revealed that ~ 90% of all drugs in the established and newly approved drug lists were administered systemically (oral or intravenous). Meanwhile, the portion of biologics (molecular weight > 1 kDa) was 15 times greater in the newly approved list than established drugs. Additionally, there was a 4.5-fold increase in the number of compounds with a high calculated partition coefficient (cLogP > 3) and a high total polar surface area (> 75 Å) in the newly approved drug vs. the established category. Further, prodrugs in established or newly approved lists were found to be converted to active compounds via hydrolysis, demethylases, and kinases. The contribution of cytochrome P450 (CYP) 3A4, as the major biotransformation pathway, has increased from 40% in the established drug list to 64% in the newly approved drug list. Moreover, the role of CYP1A2, CYP2C19, and CYP2D6 were decreased as major metabolizing enzymes among the newly approved medications. Among non-CYP major metabolizers, the contribution of alcohol dehydrogenases/aldehyde dehydrogenases (ADH/ALDH) and sulfotransferases decreased in the newly approved drugs compared with the established list. Furthermore, the highest contribution among uptake and efflux transporters was found for Organic Anion Transporting Polypeptide 1B1 (OATP1B1) and P-glycoprotein (P-gp), respectively.
CONCLUSIONS
The higher portion of biologics in the newly approved drugs compared with the established list confirmed the growing demands for protein- and antibody-based therapies. Moreover, the larger number of hydrophilic drugs found in the newly approved list suggests that the probability of toxicity is likely to decrease. With regard to CYP-mediated major metabolism, CYP3A5 showed an increased involvement owing to the identification of unique probe substrates to differentiate CYP3As. Furthermore, the contribution of OATP1B1 and P-gp did not show a significant shift in the newly approved drugs as compared to the established list because of their broad substrate specificity.
Topics: Animals; Biological Transport; Biotransformation; Drug Approval; Humans; Prescription Drugs; United States; United States Food and Drug Administration
PubMed: 30972694
DOI: 10.1007/s40262-019-00750-8 -
Alimentary Pharmacology & Therapeutics Jan 2003: To quantify through systematic review the pharmacokinetic profiles of the oral delayed release and sustained release mesalazine (5-aminosalicylate, 5ASA) formulations... (Review)
Review
AIM
: To quantify through systematic review the pharmacokinetic profiles of the oral delayed release and sustained release mesalazine (5-aminosalicylate, 5ASA) formulations (Asacol, Salofalk, Mesasal, Claversal, Pentasa) and pro-drugs (sulfasalazine, olsalazine, balsalazide) used in the management of ulcerative colitis.
METHODS
: Selected articles had: (1) adult healthy volunteers or patients with ulcerative colitis and (2) quantification of pharmacokinetic data to include, at a minimum, urinary excretion of total 5ASA [5ASA plus N-Acetyl-5ASA (N-Ac-5ASA)].
DATA COLLECTION AND ANALYSIS
: Pharmacokinetic data (Tmax, Cmax, AUC, urinary excretion, faecal excretion) of 5ASA, its major metabolite N-Acetyl-5ASA, total 5ASA, and the parent pro-drug compounds was extracted.
MAIN RESULTS
: The summary results for urinary excretion of total 5ASA over 24-96 h in all subjects (either mean or median) were: sulfasalazine mean 11-33% or median 22%; olsalazine mean 14-31% or median 16-27%; balsalazide mean 12-35% or median 20%; Asacol mean 10-35% or median 18-40%; Pentasa mean 15-53% or median 23-34%; Salofalk, Mesasal and Claversal mean 27-56% or median 31-44%. The summary results for faecal excretion of total 5ASA over 24-96 h in all subjects (either mean or median) were: sulfasalazine mean 23-75% or median 38%; olsalazine mean 47-50% or median 17-36%; balsalazide mean 46% or median 22%; Asacol mean 40-64% or median 20-56%; Pentasa mean 12-51% or median 39-59%; Salofalk, Mesasal and Claversal mean 37-44% or median 23-35%.
CONCLUSIONS
: The systemic exposure to 5ASA, as measured by urinary excretion of total 5ASA, and the faecal excretion of total 5ASA is comparable for all oral mesalazine formulations and pro-drugs. Thus, selection of a mesalazine therapy for the treatment of ulcerative colitis should be based on other factors such as efficacy, dose-response, toxicity of the parent compound and its metabolites, compliance issues related to dose forms and dosing schedules, and costs.
Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Feces; Humans; Mesalamine; Prodrugs
PubMed: 12492730
DOI: 10.1046/j.1365-2036.2003.01408.x -
Molecules (Basel, Switzerland) May 2022Bile acids (BAs) are important steroidal molecules with a rapidly growing span of applications across a variety of fields such as supramolecular chemistry, pharmacy, and... (Review)
Review
Bile acids (BAs) are important steroidal molecules with a rapidly growing span of applications across a variety of fields such as supramolecular chemistry, pharmacy, and biomedicine. This work provides a systematic review on their transport processes within the enterohepatic circulation and related processes. The focus is laid on the description of specific or less-specific BA transport proteins and their localization. Initially, the reader is provided with essential information about BAs' properties, their systemic flow, metabolism, and functions. Later, the transport processes are described in detail and schematically illustrated, moving step by step from the liver via bile ducts to the gallbladder, small intestine, and colon; this description is accompanied by descriptions of major proteins known to be involved in BA transport. Spillage of BAs into systemic circulation and urine excretion are also discussed. Finally, the review also points out some of the less-studied areas of the enterohepatic circulation, which can be crucial for the development of BA-related drugs, prodrugs, and drug carrier systems.
Topics: Bile Acids and Salts; Bile Ducts; Carrier Proteins; Enterohepatic Circulation; Liver
PubMed: 35566302
DOI: 10.3390/molecules27092961 -
Toxicology Mar 2022Tripterygium wilfordii Hook f. has a long history of use in Chinese medicine. Triptolide (TP), as its main pharmacological component, has been widely explored in various... (Review)
Review
Tripterygium wilfordii Hook f. has a long history of use in Chinese medicine. Triptolide (TP), as its main pharmacological component, has been widely explored in various diseases, including systemic lupus erythematosus, rheumatoid arthritis and cancer. However, due to its poor water solubility, limited therapeutic range and multi-organ toxicity, TP's clinical application has been greatly hampered. To improve its clinical potential, many attenuated drug combinations have been developed based on its toxicity mechanism and targeted delivery systems aimed at its water-solubility and structure. This review, conducted a systematic review of TP detoxification strategies including drug combination detoxification strategies from metabolic and toxic mechanisms, as well as drug delivery detoxification strategies from the prodrug strategy and nanotechnology. Many detoxification strategies have demonstrated promising potential in vitro and in vivo due to previous extensive studies on TP. Therefore, summarizing and discussing TP detoxification strategies for clinical problems can serve as a reference for developing novel TP detoxification strategies, and provide opportunities for future clinical applications.
Topics: Diterpenes; Drug Combinations; Epoxy Compounds; Phenanthrenes; Water
PubMed: 35202762
DOI: 10.1016/j.tox.2022.153134 -
Pain Physician Nov 2017Abuse-deterrent formulations (ADFs) represent one novel strategy for curbing the potential of opioid abuse. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Abuse-deterrent formulations (ADFs) represent one novel strategy for curbing the potential of opioid abuse.
OBJECTIVE
We aim to compare and contrast the characteristics and applications of current abuse-deterrent opioid products in clinical practice.
METHODS
Literature searches were conducted in databases (Pubmed Medline, International Pharmaceutical Abstracts, Google Scholar) and official reports. Relevant data were screened and organized into: 1) epidemiology of opioid abuse, 2) mitigation strategies for reducing opioid abuse, 3) development of ADFs, and 4) clinical experience with these formulations.
RESULTS
Increasing trends of opioid abuse and misuse have been reported globally. There are 5 types of abuse-deterrent opioid products: physical chemical barrier, combined agonist/antagonist, sequestered aversive agent, prodrug, and novel delivery system. The advantages and disadvantages of the 5 options are discussed in this review. A total of 9 products with abuse-deterrent labels have been approved by the Food and Drug Administration (FDA). The rates of abuse, diversion, and overdose deaths of these new products are also discussed. A framework for collecting in-time data on the efficacy, benefit and risk ratio, and cost-effectiveness of these new products is suggested to facilitate their optimal use.
LIMITATIONS
The present review did not utilize systematic review standards or meta-analytic techniques, given the large heterogeneity of data and outcomes reviewed.
CONCLUSIONS
ADFs provide an option for inhibiting the abuse or misuse of oral opioid products by hindering extraction of the active ingredient, preventing alternative routes of administration, or causing aversion. Their relatively high costs, uncertain insurance policies, and limited data on pharmacoeconomics warrant collaborative monitoring and assessment by government agencies, pharmaceutical manufacturers, and data analysis services to define their therapeutic role in the future.
KEY WORDS
Opioid abuse, abuse-deterrent formulations, ADF, post-marketing, FDA guidance, cost impact, abuse liking, physician attitude, generic abuse-deterrent formulation, clinical application.
Topics: Analgesics, Opioid; Chemistry, Pharmaceutical; Drug Compounding; Humans; Opioid-Related Disorders; Prescription Drug Misuse
PubMed: 29149148
DOI: No ID Found