Ketorolac pharmacodynamics

The high prevalence of opioid addiction and the shortcomings of systemic opioids has increased the pace of the search for alternative methods of pain management. The local delivery of pain medications has started to be used as a tool for pain management and to decrease the use of systemic opioids for these patients. Here, we explored an in-situ polymerizable hydrogel system for the local delivery of analgesics and nonsteroid anti-inflammatory drugs (NSAID) for orthopaedic applications. We synthesized a series of methacrylated oligomeric polyethylene glycol-co-lactic acid polymer using microwave radiation for the delivery of bupivacaine hydrochloride as an analgesic and ketorolac tromethamine as an NSAID...

The opioid epidemic has forced practitioners to look to other means for pain control. This has made non-steroidal anti-inflammatory medications (NSAIDs) much more prevalent. Advantageous as it might seem, a closer look at the pharmacodynamics shows that by inhibiting COX enzymes, NSAIDs are inhibiting prostaglandin which could inhibit bone healing. Our objective is to determine if NSAID use during foot and ankle arthrodesis inhibits bone healing. We reviewed the electronic database of patients who underwent foot and/or ankle arthrodesis with the inclusion criteria of fusion CPT codes...

Background: This study aimed to evaluate the impact of ketorolac on the pharmacokinetics of 5-FU and its effect on the efficacy of 5-fluorouracil (5-FU) on the HT-29 cell line. Methods: Cell culture: the HT-29 cell line was treated with different concentrations of 5-FU, ketorolac, and combination of 5-FU and ketorolac for 24 and 48 hours. The cell viability (%) was calculated by the MTT assay. Animal study: rats were randomly divided into control and pretreatment groups...

BACKGROUND: Streptococcus pneumoniae is the principal etiological agent of acute bacterial meningitis (ABM) which has fatal outcome in children and elderly. Due to poor blood-brain barrier (BBB) permeation, conventional β-lactam antibiotics fail to establish the requisite bactericidal concentration in central nervous system leading to resistance in meningeal infections. The present study intended to identify potential therapeutic alternatives against Streptococcal meningitis. METHODS: Virtual screening, pharmacokinetics/pharmacodynamics (PK/PD) and anti-bacterial evaluations were employed to screen potential drugs...

BACKGROUND: Postoperative patient-controlled analgesia provides pain relief, encourages early mobilization, and results in a shortened hospital stay. Patient-controlled analgesia involves the mixing of different types of drugs. When using patient-controlled analgesia, it is important to confirm the microbiological and physicochemical stability of each drug in a mixture to guarantee that the drug is delivered to the patient in an unaltered form. OBJECTIVES: To confirm the microbiological and physicochemical stability of various drug mixtures for intravenous patient-controlled analgesia...

OBJECTIVE: To evaluate the pharmacokinetics and pharmacodynamics, dosing, efficacy, and safety of ketorolac in postoperative patients younger than 6 months of age. METHODS: PubMed (1988-July 2020), Medline (1946-July 2020), and EBSCO Discovery Service (1988-July 2020) were searched to identify relevant published articles using the following search terms: ketorolac, neonate, infant. English-language articles evaluating the use of ketorolac in infants younger than 6 months of age were included...

AIMS: Ketorolac is a non-steroidal anti-inflammatory racemic drug with analgesic effects only attributed to its S-enantiomer. The aim of this study is to quantify enantiomer-specific maturational pharmacokinetics (PK) of ketorolac and investigate if the contribution of both enantiomers to the total ketorolac concentration remains equal between infants and adults or if a change in target racemic concentration should be considered when applied to infants. METHODS: Data were pooled from 5 different studies in adults, children, and infants, with 1020 plasma concentrations following single intravenous ketorolac administration...

The aim was to prepare intravenous fat emulsions (IFEs) of ketorolac (KTL) ester prodrugs and to investigate the pharmacokinetics and pharmacodynamics of these formulations. Three prodrugs of KTL (KTL-IS, KTL-AX and KTL-BT) were synthesized as a means to increase the lipid solubility of KTL. All KTL prodrugs with higher Log P values presented increased tendency to partition into a blank IFE using extemporaneous addition method - the encapsulation efficiency of KTL-IS IFE and KTL-BT IFE was more than 97%. The particle sizes and zeta potentials of these two formulations were comparable to that of the blank IFE...

In June 2013, the European Medicine Agency recommended limiting codeine use in paediatric patients, creating a void in managing moderate pain. We reviewed the literature published in English (1985-June 2017) on the pharmacokinetic, pharmacodynamic and safety profile of ketorolac, a possible substitute for codeine and opioids, for treating moderate-to-severe pain. We found that gastrointestinal side effects were mainly reported with prolonged use, significant bleeding was reported in adenotonsillectomy, and adverse renal effects appeared to be limited to patients with specific coexisting risk factors...

Aspirin (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) are a mainstay of therapy for the treatment of idiopathic pericarditis (IP). A comprehensive review consisting of pertinent clinical literature, pharmacokinetic, and pharmacodynamic considerations, has not been released in recent years. This review will facilitate the clinician's understanding of pharmacotherapeutic considerations for using ASA/NSAIDs to treat IP. Data were compiled using clinical literature consisting of case reports, cohort data, retrospective and prospective studies, and manufacturer package inserts...

Ketorolac tromethamine (KT) was potent to treat moderate to moderately severe pains. However, KT solutions for nasal delivery lost quickly from the nasal route. Thermo- and ion-sensitive in-situ hydrogels (ISGs) are appropriate for nasal drug delivery because the intranasal temperature maintains ∼37 °C and nasal fluids consist of plentiful cations. In this study, a novel nasal thermo- and ion-sensitive ISG of KT was prepared with thermo-sensitive poloxamer 407 (P407) and ion-sensitive deacetylated gellan gum (DGG)...

OBJECTIVE: To review the commercially available ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs), identify opportunities for therapeutic substitutions within and outside of their Food and Drug Administration (FDA)-approved indications, and identify clinically superior drugs within the class for specific indications. DATA SOURCE: A PubMed search (1992 through January 2014) was performed on the terms diclofenac, ketorolac, flurbiprofen, bromfenac, and nepafenac...

Methods of fluorescent probing, spectrophotometry and microcalorimetry were applied to investigate the alterations in biophysical parameters of erythrocytes membranes, and specifically microviscosity, surface charge, molecular organization of lipid bilayer and lipid-protein interactions under conditions of acute pain syndrome produced by experimental chemical lesion. The distinctive features of non-opiod analgesics interactions and binding to the erythrocytes membranes of rats subjected to acute nociceptive pain accompanied with oxidative stress development were investigated...

OBJECTIVE: To examine the efficacy of nepafenac in the treatment of pain and inflammation in patients after cataract surgery using evidence from controlled clinical studies. DATA SOURCES: Citations in Google Scholar, PubMed, and Web of Science from January 1, 2005, to March 25, 2013, were identified using nepafenac and cataract as search terms. STUDY SELECTION AND DATA EXTRACTION: The literature search was limited to human studies published in English...

A pharmacokinetic/pharmacodynamic, randomized, crossover, placebo-controlled study was conducted in healthy human volunteers with the primary objective of exploring the existence of a positive interaction between paracetamol 1 g and ketorolac 20 mg intravenously on experimental pain models. Further, the simplified UVB model was validated as a screening tool for analgesics or a combination of analgesics in clinical drug development. It was observed that the UVB irradiation induced primary hyperalgesia, evidenced by significant decreases of the heat pain threshold from (mean ± SD) 46...

CONTEXT: Ketorolac is one of the most potent nonsteroidal anti-inflammatory drugs and is an attractive alternative to opioids for pain management. OBJECTIVE: Development and evaluation of transdermal ketorolac film forming polymeric solution. MATERIALS AND METHODS: Eudragits(®) RLPO, RSPO and E100 as well as polyvinyl pyrrolidone K30 dissolved in ethanol were used as film forming solutions. In vitro experiments were conducted to optimize formulation parameters...

The combination of paracetamol with non-steroidal anti-inflammatory drugs (NSAIDs) is widely used; however, the nature and mechanism of their interaction are still debated. A double-blind, pharmacokinetic/pharmacodynamic, randomized, cross-over, placebo-controlled study was carried out in human healthy volunteers. The aim was to explore the existence of a positive interaction between paracetamol 1 g and ketorolac 20 mg administered intravenously on experimental pain models in human beings. The effects of the paracetamol-ketotolac combination were compared with similar doses of respective single analgesic and to placebo on the sunburn model (UVB-induced inflammation), cold pain tolerance and the nociceptive flexion reflex...

Population pharmacodynamic experiments sometime involve repeated measurements of ordinal random variables at specific time points. Such longitudinal data presents a challenge during modelling due to correlation between measurements within an individual and often mixed-effects modelling approach may be used for the analysis. It is important that these studies are adequately powered by including an adequate number of subjects in order to detect a significant treatment effect. This paper describes a method for calculating sample size for repeated ordinal measurements in population pharmacodynamic experiments based on analysis by a mixed-effects modelling approach...

PURPOSE: To evaluate the aqueous humor concentrations and cyclooxygenase (COX) inhibitory activities of nepafenac, amfenac, ketorolac, and bromfenac after topical ocular administration of Nevanac (nepafenac 0.1%), Acular LS (ketorolac 0.4%), or Xibrom (bromfenac 0.09%). SETTING: Five private ophthalmology practices throughout the United States. METHODS: Patients requiring cataract extraction were randomized to 1 of 3 treatment groups: Nevanac, Acular LS, or Xibrom...

Non-narcotic analgetics sodium diclofenac, indomethacin, naproxen, nimesulid, ketorolac, and celebrex (cytochrome P-450(2)c substrates) produce more pronounced and prolonged analgesic effect in pubertate female rats than in males. This can be related to the slower elimination of drugs from the female organism. The liver of females is characterized by a lower content of cytochrome P-450 and by less pronounced activity of amidopyrine-N-, indomethacin-O-, and naproxen-O-demethylase activity. No sex-related differences in pharmacodynamics were observed for meloxicam, and ethoricoxib, benzofurocaine, and amison, and acetylsalicylic acid, which are the substrates predominantly for CYP3A...