Classifications
Fazal-I-Akbar Danish, Ahmed Ehsan Rabbani in Pharmacology in 7 Days for Medical Students, 2018
Drugs with analgesic and moderate anti-inflammatory effectsPropionic acid derivativesIbuprofenKetoprofenFenoprofenFlurbiprofenCarprofenIndoprofenNaproxenOxaprozinFenamic acid derivativesMefenamic acidMeclofenamic acidFlufenamic acidTolfenamic acid
Investment Dynamics in the World of Pharma
Rebecca A. Krimins in Learning from Disease in Pets, 2020
The top-selling human drug in 2018 was Humira®, with $20.45 billion in annual sales (Group 2018). The top 50 human drugs averaged $4.94 billion in annual sales (Group 2018). The largest-selling veterinary drug is the non-steroidal anti-inflammatory drug (NSAID), Rimadyl (carprofen), with annual sales of $200 million (Bautz 2016). The 200th-largest-selling human drug, Uptravi® (selexipag), has annual sales of more than $700 million, more than triple the largest-selling veterinary drug ever marketed. Table 5.1 lists human health pharmaceutical companies with associated animal health companies.
Pharmacokinetic-Pharmacodynamic Correlations of Analgesics
Hartmut Derendorf, Günther Hochhaus in Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
Using a similar design to the above two studies, the same group was also able to demonstrate a concentration-response relationship for another NSAID, namely carprofen, when plasma concentrations were in the post-distributive phase.120 As the plasma concentrations increased so did the percent of patients responding to treatment, as judged by improvement in six clinical efficacy parameters. Sixty-nine percent of the rheumatoid patients responded when the carprofen concentrations were above 10 µg/ml, whereas only 9% responded when concentrations fell below ~2 µg/ml.
The case for complement component 5 as a target in neurodegenerative disease
Published in Expert Opinion on Therapeutic Targets, 2023
Amelia Stennett, Kallie Friston, Claire L. Harris, Adam J. M. Wollman, Agnieszka K. Bronowska, Katrina S. Madden
In 2019, a study by Mishra & Rana was published, showing four approved non-steroidal anti-inflammatory drugs: sulindac, raloxifene, oxaprozin, and carprofen to directly bind to a recombinant human C5a fragment [148]. A combination of cheminformatic and structure-based in silico approaches, all-atom molecular dynamics simulations, in addition to cell-free biophysical assays such as circular dichroism (CD), fluorescence spectroscopy, and isothermal titrational calorimetry (ITC) were employed to demonstrate this. They showed that all four ligands bound to C5a with sub-micromolar affinity (Kd ranging from 0.57 μM for sulindac to 0.71 μM for raloxifene). Upon addition of the ligands over 1–100 μM range, substantial conformational alterations in C5a were observed. At low concentrations (≤1 μM), moderate conformational changes occurred in the protein, whereas increasing the concentrations beyond 10 μM completely rearranged the native structure of C5a [148]. However, none of the compounds demonstrated molecular aggregation over 1–100 μM range. Based on these results, it can be speculated that at low concentration, specific binding of the drugs at their distinct high affinity sites may induce an intrinsically disordered state within C5a, which acts as a transition state in triggering subsequent unfolding of the protein and thus might inhibit subsequent C5a-C5aR interactions. However, this speculation requires further corroboration from follow-up studies. It is also unknown whether these ligands may bind uncleaved C5, or whether such binding may prevent cleavage.
Correction of heat-induced susceptibility changes in respiratory-triggered 2D-PRF-based thermometry for monitoring of magnetic resonance-guided hepatic microwave ablation in a human-like in vivo porcine model
Published in International Journal of Hyperthermia, 2022
Bennet Hensen, Susanne Hellms, Christopher Werlein, Danny Jonigk, Phillip Alexander Gronski, Inga Bruesch, Regina Rumpel, Eva-Maria Wittauer, Florian W. R. Vondran, Dennis L. Parker, Frank Wacker, Marcel Gutberlet
MR-guided MWA was performed 30–34 days after liver resection. Anesthesia was induced via central venous catheter in the V. cava superior with propofol (10 mg/kg) (Narcofol®, CP Pharma, Germany). The animals were intubated and mechanically ventilated with an individualized isoflurane inhalation (air–oxygen mixture 1:1) for maintenance of general anesthesia. The breathing rate was set to 12 breaths/min and a ventilation volume of 10 mL/kg per breath, whereas the medium heart rate amounted to 105 beats/min. The depth of anesthesia was continuously monitored. The animals were placed in head first supine-position (Figure 1). For analgesia the animals were injected with 4 mg/kg carprofen (Rimadyl®, Zoetis, USA) intravenously at the time of induction of anesthesia. Prior to each puncture of the liver with the microwave applicator, the animals received 1 mg/kg lidocaine as local anesthetic at the site of skin penetration. At the end of the MRI experiments, the animals were euthanized in deep anesthesia by intravenous injection of T61 (MSD Tiergesundheit, Unterschleißheim, Germany).
Protective effects of carbonic anhydrase inhibition in brain ischaemia in vitro and in vivo models
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Ilaria Dettori, Irene Fusco, Irene Bulli, Lisa Gaviano, Elisabetta Coppi, Federica Cherchi, Martina Venturini, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Alessio Nocentini, Claudiu T. Supuran, Anna Maria Pugliese, Felicita Pedata
Focal cerebral ischaemia was induced permanently by intraluminal MCAo in the right hemisphere. The animals were anaesthetised with 5.0% isoflurane (Baxter International) and spontaneously inhaled 1.0–2.0% isoflurane in air by the use of a mask. Body core temperature was maintained at 37 °C with a recirculating pad and K module and was monitored via an intrarectal type T thermocouple (Harvard, Kent, UK). The surgical procedure to occlude the MCA consisted in insertion of a 4–0 nylon monofilament (Doccol corporation, USA), via the external carotid artery into the internal carotid artery in order to block the origin of the MCA according to the procedure described by28. Carprofen (5 mg/kg) was administered intraperitoneally (i.p.) to reduce post-operative pain. The sham operation was conducted by inserting the filament into the internal carotid artery and immediately withdrawing it.
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