Pharmacological characteristics of AFP-168 (tafluprost), a new prostanoid FP receptor agonist, as an ocular hypotensive drug

Takagi, Yasutaka; Nakajima, Tadashi; Shimazaki, Atsushi; Kageyama, Masaaki; Matsugi, Takeshi; Matsumura, Yasushi; Gabelt, B’Ann T.; Kaufman, Paul L.; Hara, Hideaki

doi:10.1016/j.exer.2003.12.007

Cited by 140 publications

(160 citation statements)

References 32 publications

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“…a , partial agonist. 506 isopropyl ester of fluprostenol, named travoprost (Hellberg et al, 2001) and tafluprost (Takagi et al, 2004;Cirillo et al, 2007). Comparisons between these drugs are widely available and are not reviewed here.…”

Section: Fp Receptorsmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

Woodward

Jones

Narumiya³

2011

Pharmacol Rev

389

414

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Section: Fp Receptorsmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

Woodward

Jones

Narumiya³

2011

Pharmacol Rev

389

414

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“…Tafluprost (0.001-0.005%) was applied once daily for 5 days to the eyes of normotensive monkeys and had the advantage of a reduced IOP at the trough time of 24 h after dosing, whereas 0.005% latanoprost did not. Tafluprost also had less stimulating effects on melanogenesis in vitro, whereas tafluprost acid possessed a greater affinity for the prostanoid FP-receptor than the acid form of latanoprost (Takagi et al, 2004). Recent results of a clinical study involving healthy volunteers also showed well tolerability of 0.0025 and 0.005% tafluprost ophthalmic solutions and greater IOP reduction by 0.005% tafluprost than 0.005% latanoprost (Sutton et al, 2007).…”

mentioning

confidence: 74%

“…The quantitative similarity in the radioactivity concentration-time curves of the iris/ciliary body and aqueous humor suggests rapid exchange of drug-derived material between the two tissues. Such an exchange would assist in increasing uveoscleral outflow, which is considered to be the main mechanism for the ocular hypotensive effect achieved by tafluprost (Takagi et al, 2004), as it is for related prostaglandins (Stjernschantz et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown that tafluprost is superior to latanoprost in several important pharmacological criteria (Nakajima et al, 2003;Takagi et al, 2004). Thus, in both ocular normotensive and laser-induced ocular hypertensive monkeys, a single instillation of 0.0025% tafluprost solution lowered IOP significantly more than 0.005% latanoprost.…”

mentioning

confidence: 97%

“…Tafluprost decreases the IOP in vivo mainly by increasing the uveoscleral outflow by up to 65% (Takagi et al, 2004). Studies have shown that tafluprost is superior to latanoprost in several important pharmacological criteria (Nakajima et al, 2003;Takagi et al, 2004).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Disposition and Metabolism of a Novel Prostanoid Antiglaucoma Medication, Tafluprost, Following Ocular Administration to Rats

Fukano

Kawazu²

2009

Drug Metab Dispos

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ABSTRACT:The disposition and metabolism of tafluprost, an ester prodrug of the 15,15-difluoro-prostaglandin F 2␣ antiglaucoma agent, have been studied in rats after ocular administration. Radioactivity was absorbed very rapidly into the eye and systemic circulation after a single ocular dose of 0.005% [ 3 H]tafluprost ophthalmic solution, with maximum levels in plasma and most eye tissues occurring within 15 min. The absorption ratio of radioactivity was approximately 75%, suggesting the high availability of ocular administration of tafluprost. Approximately 10% of the dose was present in cornea at this time, and radioactivity concentrations in this tissue exceeded those in aqueous humor and iris/ciliary body throughout the 24-h study period. After repeated daily ocular doses, radioactivity levels remained greatest in cornea, followed by iris/ciliary body that replaced aqueous humor as the eye tissue containing the second highest radioactivity concentration. In female rats, radioactivity was excreted equally between urine and feces after a single ocular dose, whereas in male rats more was excreted in feces, reflecting the greater biliary excretion in males rats (50% dose) compared with females rats (33% dose). Tafluprost was extensively metabolized in the rat, such that intact prodrug was not detected in plasma, tissues, or excreta by radio-high-performance liquid chromatography. On the other hand, the active moiety, tafluprost acid, was the only noteworthy radioactive component in cornea, aqueous humor, and iris/ciliary body for at least 8 h after the ocular dose, and it was also a major plasma metabolite in early time points. The gender differences in conjugation reactions resulted in the differences in the excretion.

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Eicosanoid Pathway Modulators: Prostaglandins, Prostacyclin, and Thromboxane

Mazaleuskaya

Ricciotti

2021

Burger's Medicinal Chemistry and Drug Discovery

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Prostanoids (prostaglandins, prostacyclin, and thromboxane) are bioactive lipids, members of the eicosanoid class of compounds, derived from arachidonic acid (AA). They are involved in controlling homeostatic and pathophysiological processes. Their biosynthesis is the result of the coordinated actions of several enzymes. Cyclooxygenases (COXs) catalyze the committed step in the conversion of AA into prostanoids. There are two COX isozymes: the constitutive COX‐1 and the inducible COX‐2, both of which have different patterns of expression and biological functions. COX‐1 and COX‐2 are the targets of traditional nonsteroidal anti‐inflammatory drugs (tNSAIDs), which are used to relieve pain, fever and inflammation. Despite their clinical efficacy, tNSAIDs cause side effects, particularly in the gastrointestinal (GI) tract. NSAIDs selective for COX‐2 inhibition (coxibs) were purposefully designed to spare GI side effects, but predisposed patients to increased cardiovascular (CV) risks. The GI and CV complications from existing NSAIDs prompted interest in the downstream effectors of the COX enzymes as novel drug targets. This article describes various safety issues with tNSAIDs and coxibs, and discusses the current development of novel classes of drugs targeting the AA pathway, including nitric oxide‐releasing and hydrogen sulfide‐releasing NSAIDs, inhibitors of prostanoid synthases, dual inhibitors, and prostanoid receptor agonists and antagonists.

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Pharmacological characteristics of AFP-168 (tafluprost), a new prostanoid FP receptor agonist, as an ocular hypotensive drug

Cited by 140 publications

References 32 publications

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

Disposition and Metabolism of a Novel Prostanoid Antiglaucoma Medication, Tafluprost, Following Ocular Administration to Rats

Eicosanoid Pathway Modulators: Prostaglandins, Prostacyclin, and Thromboxane

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