Prostaglandin E2 Inhibition and Aqueous Concentration of Ketorolac 0.4% (Acular LS) and Nepafenac 0.1% (Nevanac) in Patients Undergoing Phacoemulsification

Bucci, Frank A.; Waterbury, L. David; Amico, L.M.

doi:10.1016/j.ajo.2007.02.034

Cited by 36 publications

(25 citation statements)

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“…8 Because PGE 2 is a known mediator of ocular inflammation, PGE 2 levels are frequently assayed to quantify the amount of inflammation under specific study conditions. 13,14,15 In particular, the study by Bucci et al 5 reports the aqueous humor PGE 2 levels after ketorolac and nepafenac application. However, the study had several design limitations.…”

Section: Discussionmentioning

confidence: 97%

In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac

Walters¹,

Raizman²,

Ernest³

et al. 2007

Journal of Cataract and Refractive Surgery

104

101

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Section: Discussionmentioning

confidence: 97%

In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac

Walters¹,

Raizman²,

Ernest³

et al. 2007

Journal of Cataract and Refractive Surgery

104

101

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“…In a similar study in which the dosing regimen was simulated consistent with our clinical practice, we observed that aqueous ketorolac concentrations were significantly higher than nepafenac and amfenac concentrations. 2 In addition, we found that the mean aqueous PGE 2 levels were 50% lower in patients treated with ketorolac than in those treated with nepafenac (159.5 G 114.7 pg/mL versus 322.3 G 197.8 pg/ mL; P!.001). 2 Walters et al criticized our study for using a nonstandard dosing regimen.…”

mentioning

confidence: 91%

“…2 In addition, we found that the mean aqueous PGE 2 levels were 50% lower in patients treated with ketorolac than in those treated with nepafenac (159.5 G 114.7 pg/mL versus 322.3 G 197.8 pg/ mL; P!.001). 2 Walters et al criticized our study for using a nonstandard dosing regimen. However, our regimen (4 times a day for 2 days followed by pulse dosing 4 times during the 90 minutes before surgery) mimicked our clinical practice, which is supported by other studies clearly demonstrating the improved efficacy of a 1-day or 3-day preoperative course of topical NSAIDs in conjunction with a pulse dosing strategy just before surgery.…”

mentioning

confidence: 91%

Pharmacokinetics and pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac

Bucci¹,

Waterbury²

2008

Journal of Cataract and Refractive Surgery

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et al. 1 reported that aqueous nepafenac concentrations were significantly higher than those of ketorolac and bromfenac in patients administered a single drop of the nonsteroidal antiinflammatory drug (NSAID) before cataract surgery. In addition, they noted that prostaglandin E 2 (PGE 2 ) levels were highly variable and ''lacked meaningful interpretation.'' In a similar study in which the dosing regimen was simulated consistent with our clinical practice, we observed that aqueous ketorolac concentrations were significantly higher than nepafenac and amfenac concentrations. 2 In addition, we found that the mean aqueous PGE 2 levels were 50% lower in patients treated with ketorolac than in those treated with nepafenac (159.5 G 114.7 pg/mL versus 322.3 G 197.8 pg/ mL; P!.001). 2 Walters et al. criticized our study for using a nonstandard dosing regimen. However, our regimen (4 times a day for 2 days followed by pulse dosing 4 times during the 90 minutes before surgery) mimicked our clinical practice, which is supported by other studies clearly demonstrating the improved efficacy of a 1-day or 3-day preoperative course of topical NSAIDs in conjunction with a pulse dosing strategy just before surgery. 3 The Walters et al. study included a number of conclusions that did not appear substantiated by the reported data. Nepafenac levels alone or in combination with amfenac were compared with those of the active study drugs, and it was suggested that nepafenac served as a reservoir for continued amfenac production. However, the data presented by Walters et al. demonstrate that nepafenac did not inhibit cyclooxygenase (COX)-2 activity and the halfmaximum inhibitory concentration (IC 50 ) for COX-1 inhibition was approximately 100 times higher than the achievable aqueous concentration. This indicates that nepafenac is a prodrug with no in vivo COX inhibitory activity and, therefore, clinically irrelevant. More important, only a fraction of nepafenac was converted to amfenac, despite a steep decrease in aqueous nepafenac concentration. These findings demonstrate that the rate of nepafenac elimination from aqueous humor was far greater than the rate of its conversion to amfenac. Therefore, the nepafenac levels do not translate to an amfenac reservoir in the aqueous humor.Walters et al. concluded that the exposure to amfenac and ketorolac was similar and significantly higher than the exposure to bromfenac. This conclusion is invalid because the study design ignored the variability of NSAIDs' pharmacokinetics. Consequently, the overall exposure was determined by including timepoints of concentration assessments that represented each study drug at a different stage in the pharmacokinetic curve.Based on the pharmacokinetic studies reported by Walters et al., amfenac was stated to have a longer near-maximum concentration than ketorolac; it was suggested that it had a prolonged duration of action relative to other topical drugs in this class. However, the Walters et al. study lacked the data to support this conclusion as amfenac conce...

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“…Bunlardan biri olan topikal nonsteroidal antiinflamatuar ajanlar (NSAİA), ayrıca katarakt veya refraktif cerrahi sonrası görülen ağrı ve enflamasyonu, prostaglandin (PG) sentezini inhibe ederek azaltmak için kullanılmaktadır. [2][3][4][5] Oftalmolojide NSAİA kullanılan diğer durumlar arasında katarakt cerrahisi sırasında intraoperatif miyozisin engellenmesi, katarakt cerrahisi sonrası kistoid maküler ödemin engellenmesi ve oluştuğunda kistoid maküler ödemin tedavisi sayılabilir. 6 Allerjenler konjonktivada eş zamanlı olarak histamin salınımını ve araşidonik asidin PG'ye dönüşümünü tetiklerler.…”

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Comparison of the Effects of Two Different Concentrations of Ketorolac Tromethamine Solutions in Patients with Allergic Conjunctivitis

Ulaş¹,

Balbaba²,

Çankaya³

2012

Turkiye Klinikleri J Med Sci

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Ö ÖZ ZE ET T A Am ma aç ç: : İki farklı konsantrasyonda ketorolak trometamin (KT) içeren oftalmik solüsyonların (%0,5 ve %0,4), allerjik konjonktivitli olgularda klinik etkinlik ve yan etkilerininin araştırılması. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Allerjik konjonktivit dışında herhangi bir sistemik veya göz hastalığı bulunmayan ve yaşları 24-35 arasında değişen 20'si kadın 16'sı erkek toplam 36 olgu çalışmaya dahil edildi. Çalışmaya dahil edilen olguların randomize olarak bir gözlerine %0,5, diğer gözlerine %0,4 konsantrasyonlu KT oftalmik solüsyon tedavisi uygulandı. Olgular bir hafta sonra değerlendirildi ve tedavi öncesi ve sonrası belirtiler ve bulgular ile ilaca bağlı yan etkiler ve ilaç toleransı karşılaş-tırıldı. B Bu ul lg gu ul la ar r: : Allerjik konjonktivitli olgularda, farklı konsantrasyonlardaki KT solüsyonları ile yapılan tedavi sonrasında belirtiler ve bulgular anlamlı ölçüde düzelse de, hastaların %77,8'inde tam bir klinik düzelme saptanmadı. Her iki konsantrasyondaki KT solüsyonu ile ilgili herhangi bir yan etki ve tedaviyi aksatmaya neden olacak düzeyde belirgin bir ilaç tolerans sorunu saptanmazken, olguların %41,7'si her iki ilacın eşit düzeyde, %50,0'si %0,4'lük konsantrasyonun daha az, %8,3'ü ise %0,5'lik konsantrasyonun daha az yanmaya neden olduğunu bildirdi. S So on nu uç ç: : Her iki konsantrasyondaki KT solüsyonları da allerjik konjonktivit tedavisinde kısmi düzelme sağladı ve yan etkiye neden olmadı. İlaç toleransının %0,4'lük KT konsantrasyonlu solüsyonda daha iyi olduğu ve %0,4'lük KT solüsyonunun, %0,5 konsantrasyonlu KT solüsyonla aynı etkinlikte kullanılabileceği belirlendi. Ancak, azalmış olmasına rağmen ilaç tolerans sorununun yine devam ettiği gözlemlendi.A An na ah ht ta ar r K Ke el li im me el le er r: : Ketorolak trometamin; konjonktivit, allerjik A AB BS ST TR RA AC CT T O Ob bj je ec ct ti iv ve e: To evaluate the clinical efficacy and side effects of two different concentrations of KT solutions (0.5% and 0.4%) in allergic conjunctivitis patients. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : Thirty-six patients (20 females and 16 males) who did not have any ocular or systemic disorder other than allergic conjunctivitis were enrolled in the study, ages of the patients ranged from 24 to 35 years. Patients randomly received treatment to one eye with KT 0.4% and to the other eye with KT 0.5%. Patients were evaluated after one week and symptoms, signs before and after the treatment, drug related adverse effects and intolerance were assessed. R Re es su ul lt ts s: : Although the signs and symptoms of the allergic conjunctivitis in both eyes improved significantly, it did not recover completely in 77.8% of the patients. Either concentrations of the KT solutions did not cause any adverse effect or significant intolerance that might cause cessation of treatment. Comparable mild drug intolerance for both KT solutions, was reported by 41.7% of the cases while 50.0% of the patients reported better tolerance for KT 0.4%, 8.3% of the patients repor...

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Prostaglandin E2 Inhibition and Aqueous Concentration of Ketorolac 0.4% (Acular LS) and Nepafenac 0.1% (Nevanac) in Patients Undergoing Phacoemulsification

Cited by 36 publications

References 1 publication

In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac

In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac

Pharmacokinetics and pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac

Comparison of the Effects of Two Different Concentrations of Ketorolac Tromethamine Solutions in Patients with Allergic Conjunctivitis

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