A Double-Blind Placebo-Controlled Comparison of a Novel Formulation of Intravenous Diclofenac and Ketorolac for Postoperative Third Molar Extraction Pain

Christensen, Kyle S.; Daniels, Stephen E.; Bandy, Donald P.; Ernst, Cynthia C.; Hamilton, Douglas A.; Mermelstein, Fred H.; Wang, Jianyuan; Carr, Daniel B.

doi:10.2344/0003-3006-58.2.73

Cited by 29 publications

(28 citation statements)

References 17 publications

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“…Diclofenac is used in moderate to severe pain following third molar extraction and it could be used in an intravenous form in risk population groups such as the elderly and renal insufficiency, postoperative anticoagulation which uses ketorolac as the only choice for the moderate to severe acute pain. Very similar effects were shown when transdermal diclofenac patches were used compared to oral administration [99,100].…”

Section: Analgesic Monotherapy Versus Combined Therapy In Dental Pracsupporting

confidence: 50%

Analgesics Use in Dentistry

Krasniqi¹,

Daci²

2017

Pain Relief - From Analgesics to Alternative Therapies

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Pain is a protective warning sign activated by tissue damage during different pathological processes. The clinical manifestation of pain is individual, multifactorial and very complex and requires the implementation of sound pharmacological approaches. The treatment of odontogenic pain is focused not only in the relief of pain but also in the suppression of causes of pain, mainly the inflammation. Acting as inhibitors of pain mechanism, analgesics are used for symptomatic treatment of pain. There are several groups of analgesic drugs used in dentistry practice and most frequent are nonsteroidal anti-inflammatory drugs (NSAIDs) and aniline analgesics. The contemporary strategies for the treatment of odontogenic pain are focused in analgesic drug combinations, which are more effective and have a better safety profile. Ibuprofen and acetaminophen agents are considered gold standard of dental analgesia for mild to moderate intensity of pain, while in moderate to severe pain the use of individual opioid analgesics or combination of opioid and nonopioid analgesics is recommended. The treatment of pain in children and elderly patients is associated with some limitations accompanied with safety concerns and dose reduction. Treatment of pain in dentistry is focused in achieving the satisfactory level of analgesia at low doses possible.

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Section: Analgesic Monotherapy Versus Combined Therapy In Dental Pracsupporting

confidence: 50%

Analgesics Use in Dentistry

Krasniqi¹,

Daci²

2017

Pain Relief - From Analgesics to Alternative Therapies

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“…In two separate double-blind placebo-controlled trials in patients undergoing third-molar extraction, HPbCD-diclofenac had a faster onset of pain relief than either Voltarol 21 or ketorolac. 24 More recently, HPbCDdiclofenac showed a faster onset of action than IV ketorolac in a population of patients having undergone orthopedic surgery. 25 The lower incidence of thrombophlebitis with HPbCD-diclofenac compared with Voltarol and subsequent reduced need for treatment of adverse events, as well as HPbCD-diclofenac's lack of need for reconstitution, dilution, and buffering prior to each dose compared with Voltarol provide support for potential cost savings with HPbCD-diclofenac compared with Voltarol.…”

Section: Discussionmentioning

confidence: 99%

Single‐Dose and Multiple‐Dose Pharmacokinetics and Dose Proportionality of Intravenous and Intramuscular HPβCD‐Diclofenac (Dyloject) Compared with Other Diclofenac Formulations

Mermelstein¹,

Hamilton²,

Wright

et al. 2013

Pharmacotherapy

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STUDY OBJECTIVE To evaluate single-and repeated-dose pharmacokinetics (PK) and dose proportionality of hydroxypropyl-b-cyclodextrin (HPbCD)-diclofenac compared with Voltarol after intravenous (IV) and intramuscular (IM) administration. DESIGN Study 1: Single-dose randomized four-way crossover study. Study 2: Multiple-dose randomized three-way crossover study. SETTING Clinical research center. SUBJECTS Healthy adult volunteers. INTERVENTION Study 1: Subjects received HPbCD-diclofenac and Voltarol, IV and IM, with a 5-day washout between treatment periods. Study 2: Subjects received two doses of IV HPbCD-diclofenac and oral Cataflam once every 6 hours for four doses with a 48-hour washout period between treatment periods. MEASUREMENTS AND MAIN RESULTS Study 1: IV HPbCD-diclofenac had a higher peak plasma concentration (C max ) and earlier time to reach maximum plasma concentration (T max ), but equivalent plasma exposure (area under the curve from time zero to t [AUC 0-t ]) to IV Voltarol. The geometric mean ratio of HPbCD-diclofenac (IV) to Voltarol (IV) for AUC 0-t was 106.27%. The geometric mean ratio of HPbCD-diclofenac (IM) to Voltarol (IM) for AUC 0-t was 110.91%. The geometric mean ratio of HPbCD-diclofenac (IV) to HPbCD-diclofenac (IM) for AUC 0-t was 101.25%. The geometric mean ratio of HPbCD-diclofenac (IM) to Voltarol (IV) for AUC 0-t was 104.96%. Study 2: C max for diclofenac was 2904 and 6031 ng/ml after the first IV dose of 18.75 and 37.5 mg HPbCD-diclofenac, respectively, and was 3090 and 5617 ng/ml after the fourth dose, indicating no accumulation. Plasma exposures to 18.75 mg (866 ngÁhour/ml) and 37.5 mg (1843 ngÁhour/ml) IV HPbCD-diclofenac bracketed that of oral Cataflam 50 mg (1473 ngÁhour/ml). CONCLUSIONS Study 1: Bioavailability in terms of AUC after IV administration was equivalent for HPbCD-diclofenac compared with Voltarol and after IM administration of HPbCD-diclofenac and Voltarol. Bioavailability in terms of AUC after IM administration of HPbCD-diclofenac was equivalent to IV administration of HPbCD-diclofenac and IV administration of Voltarol. Study 2: HPbCDdiclofenac showed dose proportionality after single-and multiple-dose administration and no accumulation of HPbCD-diclofenac. HPbCD-diclofenac was safe and well tolerated following IV and IM administration.

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“…14 In the development program for HPbCD diclofenac, a single 37.5 mg dose was significantly more efficacious than placebo in a molar-extraction pain model. 15 Subsequently, a randomized, multiple-dose trial demonstrated the safety and superior efficacy, relative to placebo, of HPbCD diclofenac 18.75 and 37.5 mg when used for acute moderate and severe pain after major abdominal or pelvic surgery. 16 The objective of the current trial was to investigate HPbCD diclofenac for treatment of moderate and severe pain after elective orthopedic surgery.…”

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confidence: 99%