74103-06-3 Usage
Chemical properties
It is crystallized in ethyl acetate - ether with a melting point of 160~161 degrees centigrade.The maximum absorption of UV (methanol):245,312m (epsilon 7080,17400). PKa3.49 + 0.02.Acute toxic LD50 mice (mg/kg): about 200 of oral administration. .(+) - configuration: crystallized from hexane ethyl acetate with the melting point of 174 degrees centigrade;The melting point is 154 156 degrees centigrade. [α]D+173° (C=1, methanol).(-) - configuration: crystallizzed from hexane ethyl acetate with melting point at 169~170 degrees centigrade; melting point is 153~155 degrees centigrade. [α]D-176° (C=1, methanol).
Pharmacological action
Ketorolac is also called ketorolac, acular and Ketorolac Tromethamine. It is a non steroid analgesic and anti-inflammatory drug, a derivative of pyrrolidone.The chemical structure and pharmacological action is similar to Tolectin, Zoaesthetic acid and Indometacin. By inhibiting cyclooxygenase, it inhibits the synthesis and release of prostaglandins, and produces anti-inflammatory effects. It can reduce the temperature induced by heat source, which is related to the inhibition of the synthesis of prostaglandin in the central nervous system.It has strong analgesic and moderate anti-inflammatory antipyretic and inhibition of platelet aggregation, and has no inhibition of respiration and addiction. In animal experiments, the analgesic effect is stronger than aspirin, indomethacin and naproxen.It is equal to or better than the anti-inflammatory effect of naproxen and indomethacin, phenylbutazone,Its antipyretic effect on rats are stronger than aspirin and phenylbutazone and the same with indomethacin and naproxen.It inhibits the platelet aggregation induced by arachidonic acid and collagen.But it does not inhibit the induction of adenosine diphosphate(ADP) ..This product is quickly and completely absorbed after the intramuscular injection, and is almost completely absorbed after oral administration.Food can slow down the absorption speed, but it does not affect the degree of absorption, and the bioavailability is 80% ~ 100%. 10 minutes after intramuscular injection of 30mg, it usually relieves the pain obviously. After 50 minutes, the peak of plasma concentration is up to 2.2 g/mL.After 30~60 minutes of oral administration, the pain is obviously relieved and the concentration of plasma is peak at 1.5 to 4 hours.The plasma half-life of young people is about 5.3 hours, and for the elderly it is about 7 hours, and the analgesic effect could be maintained for 6~8 hours. 91.4% will be excreted from the urinary tract, the rest will be excreted from the excrement.In patients with renal insufficiency, the total plasma clearance rate decreases and the half-life prolongs, so the dosage should be reduced.
Clinical application: ketorolac is mainly used for short-term pain treatment including postoperative pain (such as the abdomen, chest, Urology, gynecology, Department of Stomatology, orthopedic surgery and pain) as well as the acute skeletal muscle pain caused by various causes, such as sprain, dislocation, fracture and soft tissue injury, and other pain caused by other diseases, such as postpartum pain, acute renal colic, toothache, sciatica, late cancer pain, wound pain, biliary colic, etc.. It can be used as a substitute for morphine and pethidine.
Chemical Properties
Light yellow solid
Uses
Different sources of media describe the Uses of 74103-06-3 differently. You can refer to the following data:
1. antiarrhythmic
2. prostaglandin F2a analogue
3. Ketorolac-d5 is a labeled analogue of Ketorolac, a Prostaglandin biosynthesis inhibitor. Analgesic; anti-inflammatory.
Indications
Ketorolac (Toradol), an NSAID chemically related
to indomethacin and tolmetin, is mainly used as an analgesic,
not for the treatment of inflammatory disease. It
is available in oral, parenteral, and topical formulations.
Brand name
Acular (Allergan); Toradol (Roche).
World Health Organization (WHO)
Ketorolac is a nonsteroidal anti-inflammatory agent used in the
management of moderate to severe acute post-operative pain. It remains on the
market in many countries with restrictions on its use.
Biological Functions
Ketorolac (Toradol) is an NSAID with very mild antiinflammatory
and antipyretic activity. It is a potent analgesic
for postoperative pain. Its efficacy is equivalent to
that of low doses of morphine in the control of pain. For
this reason it is often combined with opioids to reduce
opioid dose and related side effects while providing adequate
pain relief. It is also used to replace the opioids in
some patients with opioid sensitivity. The mechanism of
action of ketorolac involves the inhibition of COX and
decreased formation of prostaglandins. However, some
evidence exists that ketorolac may stimulate the release
of endogenous opioids as a part of its analgesic activity.
General Description
Ketorolac tromethamine (Toradol), marketed as a mixture of(R)- and (S)-ketorolac enantiomers, is a potent NSAID analgesicindicated for the treatment of moderately severe, acutepain. It should be noted that the pharmacokinetic dispositionof ketorolac in humans is subject to marked enantioselectivity.Thus, it is important to monitor the individual blood levelsso an accurate assessment of its therapeutic action can bemade correctly. However, it should be noted that, beingone of the conventional NSAIDs with highest risk of GIcomplications, its administration should not exceed 5 days.
Check Digit Verification of cas no
The CAS Registry Mumber 74103-06-3 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 7,4,1,0 and 3 respectively; the second part has 2 digits, 0 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 74103-06:
(7*7)+(6*4)+(5*1)+(4*0)+(3*3)+(2*0)+(1*6)=93
93 % 10 = 3
So 74103-06-3 is a valid CAS Registry Number.
InChI:InChI=1/C15H13NO3/c17-14(10-4-2-1-3-5-10)13-7-6-12-11(15(18)19)8-9-16(12)13/h1-7,11H,8-9H2,(H,18,19)
74103-06-3Relevant articles and documents
Permeability of ketorolac acid and its ester analogs (prodrug) through human cadaver skin
Roy,Manoukian
, p. 1548 - 1553 (1994)
The in vitro skin permeabilities of ketorolac acid (KA), a potent nonsteroidal analgesic, and its two ester analogs as prodrug through human cadaver skin were investigated. The two esters of KA, namely, the ethyl ester (KEE) and [(N,N-dimethylamino)carbonyl]methyl ester (KDAE), were selected. The melting temperature of the two esters was significantly lower than that of ketorolac free acid. The partition coefficients (K(D/W)) were 600, 3541, and 124 for KA, KEE, and KDAE, respectively. The enzymatic hydrolysis of KEE and KDAE by human pooled serum at 37 °C was investigated. The esters were hydrolyzed to KA by the serum esterases; the metabolic rate constants were 0.0418 and 0.0148 min-1 for KDAE and KEE, respectively. The serum half- life of KDAE was about 3 times shorter than KEE. When split-thickness cadaver skin was incubated with ester solution at 32 °C, the enzymatic hydrolysis of these esters was observed. The metabolic rate in the skin, however, was significantly lower than in the human pooled serum. The skin permeations of KA, KEE, and KDAE through heat-separated epidermis from propylene glycol (PG), PG/glyceryl monocaprylate (GMC) (9:1), and PG/Azone (19:1) vehicle mixtures were evaluated using modified Franz flow-through diffusion cells. The skin fluxes of KA, KEE, and KDAE from PG/GMC (9:1) were 50 ± 10, 15 ± 4, and 57 ± 6 μg/cm2/h, respectively. KA was detected in the receiver compartment, albeit to a lesser extent. In conclusion, KDAE appeared to be a better ester prodrug than KEE because it exhibited relatively higher skin flux and faster enzymatic hydrolysis by human serum to liberate the parent drug.
Effective mamagement of acute postoperative pain using intravenous emulsions of novel ketorolac prodrugs: in vitro and in vivo evaluations
Chen, Yong,Huang, Qian,Niu, Bixi,Qiu, Nanqing,Yin, Zongning,Yu, Yuting,Zhu, Qing,Zhuang, Xiaoxiao
, (2020/04/29)
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 97percent. The particle sizes and zeta potentials of these two formulations were comparable to that of the blank IFE. PK studies in rabbits showed significant larger AUC0-8h (646.969 ± 154.326 mg/L?h?1 for KTL-IS IFE and 559.426 ± 103.057 mg/L?h?1 for KTL-BT IFE) than that of ketorolac tromethamine (KTL-T) injectable (286.968 ± 63.045 mg/L?h?1) and approximately 2-fold increases in the elimination t1/2 over KTL-T. In a rat postoperative pain model, the paw withdrawal thresholds and the paw withdrawal latency after I.V. KTL prodrug IFEs were significantly higher than that after I.V. KTL-T at 3~4 h. Effective controlling of acute postoperative pain in a longer duration can be achieved by using non-addictive ketorolac derivatives intraveneous emulsions.
Synthesis process of ketorolac
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Paragraph 0021-0037, (2018/07/30)
The invention discloses a synthesis process of ketorolac, and relates to the technical field of medicine synthesis. The synthesis process solves the technical problems that the existing process can generate a large amount of liquid and solid wastes, and the environment protection is not facilitated. Hydrogen peroxide with side products being water is used as an oxidizing agent; malysite is used asa catalyst; a large number of manganese salts are replaced; when 1kg of ketorolac is reduced, 3.5 to 6.1kg of discharged liquid and solid wastes are reduced; the green and environment-friendly effects are achieved. Benzoyl chloride is directly used as raw materials; the one-step reaction is reduced; the synthesis process is simpler; the methyl tertiary butyl ether is used for replacing the flammable and combustible diethyl ether; the process production safety is improved. The synthesis process has the advantages that the operation is easy; the process conditions can be easily controlled; thefinal product purification and aftertreatment are simple.