Opalmon

Opalmon Mechanism of Action

Manufacturer:

Ono Pharmaceutical

Distributor:

DKSH

Marketer:

Meiji
The information highlighted (if any) are the most recent updates for this brand.
Full Prescribing Info
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Pharmacology: Mechanism of Action: Limaprost alfadex exerts potent effects on vasodilation, increase of blood flow and inhibition of platelet aggregation, and thereby has proven clinical effects on various ischemic symptoms such as ulcer, pain and feeling of coldness associated with thromboangiitis obliterans, as well as those on subjective symptoms (pain and numbness of lower legs) and gait ability associated with acquired lumbar spinal canal stenosis (in patients with bilateral intermittent claudication showing normal SLR test result).
Pharmacological Effects: Improving effect on peripheral circulatory disorder: In the experimental models with peripheral (hind limbs) circulatory disorder induced by injection of lauric acid to the femoral artery and with peripheral (tail) circulatory disorder induced by subcutaneous injection of adrenaline and ergotamine tartrate, limaprost alfadex inhibits the development of ischemic lesion (in rats).
Increasing effects on blood flow and cutaneous temperature: Limaprost alfadex increases femoral arterial blood flow and cutaneous blood flow in the hind limbs and elevates cutaneous temperature in the hind limbs. The effect of increasing blood flow is not affected by lumbar sympathectomy (in dogs).
OPALMON, when orally administered in patients with thromboangiitis obliterans, increases cutaneous temperature in the extremities (the dorsum and planta of the foot).
Effect on platelets: Inhibitory effect on platelet adhesiveness: OPALMON, when orally administered in patients with thrombotic diseases, decreases platelet adhesiveness.
Limaprost alfadex inhibited platelet adhesiveness with the 50% inhibitory concentration of 0.186 ng/mL of limaprost (in guinea-pigs, in vitro). Oral administration of limaprost alfadex also inhibits platelet adhesiveness (in guinea-pigs, ex vivo).
Inhibitory effect on platelet aggregation: OPALMON, when orally administered in patients with thrombotic diseases, inhibits platelet aggregation. The activity is equipotent with that of prostaglandin I2 (in vitro).
Limaprost alfadex inhibits platelet aggregation induced by various aggregating agents and dissociates ADP-induced platelet aggregation (in guinea-pigs, in vitro). Oral administration of limaprost alfadex also inhibits platelet aggregation (in guinea-pigs, ex vivo).
Limaprost alfadex remarkably elevates platelet cyclic AMP levels and inhibits thromboxane A2 production (in guinea-pigs, in vitro).
Antithrombotic effect: In the experimental models with thrombosis formation in the mesenteric artery induced by electric stimulation, limaprost alfadex dose-dependently increases threshold voltage of thrombosis formation (in guinea-pigs).
Increasing effect on blood flow in the nerve tissue: Limaprost alfadex improves blood flow in the cauda equina nerve tissue in a model where the cauda equina nerve was compressed by inserting a balloon into the dura mater of the 6th lumbar vertebra (in dogs).
Limaprost alfadex improves blood flow in the cauda equina nerve tissue in a model where the cauda equina nerve was compressed by inserting a silicone rubber into the 4th and 6th lumbar vertebral canals (in rats).
Limaprost alfadex improves blood flow in the sciatic nerve tissue in the midst of two ligatures in a model where the sciatic nerve of the right hind limb was ligated at two sites (in rats).
Improving effect on nerve function: Limaprost alfadex inhibits the decrease in nerve conduction velocity in a model where the cauda equina nerve was compressed by inserting a balloon into the dura mater of the 7th lumbar vertebra (in dogs).
Limaprost alfadex inhibits the prolongation in time duration of thermal stimulation-induced discharge in the muscle on the ligated femur in a model where the sciatic nerve of the right hind limb was ligated at four sites (in rats).
Improving effect on hyperalgesia: Limaprost alfadex improves hyperalgesia at the ligated side in a model where the sciatic nerve of the right hind limb was ligated at two sites (in rats).
Improving effect on gait disturbance: Limaprost alfadex improves decreased walking distance in a model where the cauda equina nerve was compressed by inserting a silicone rubber into the 4th and 6th lumbar vertebral canals (in rats).
Clinical Studies: Improvement of various ischemic symptoms such as ulcer, pain and feeling of coldness associated with thromboangiitis obliterans: The usefulness of OPALMON in patients with thromboangiitis obliterans was demonstrated in a double- blind comparative study.
OPALMON has been shown to improve various ischemic symptoms such as ulcer, pain and feeling of coldness associated with thromboangiitis obliterans, with an overall improvement rate of 56% (77/138 patients in clinical studies including double-blind comparative studies.
Improvement of subjective symptoms (pain and numbness of lower legs) and gait ability associated with acquired lumbar spinal canal stenosis (in patients with bilateral intermittent claudication showing normal SLR test result): The usefulness of OPALMON in patients with lumbar spinal canal stenosis was demonstrated in double- blind comparative studies.
The improvements of the subjective symptoms (pain and numbness of lower legs) and gait ability associated with acquired lumbar spinal canal stenosis (in patients with bilateral intermittent claudication showing normal SLR test result) were demonstrated in patients treated for six weeks in clinical studies including double-blind comparative studies, and an overall improvement rate was 56% (94/168 patients).
Pharmacokinetics: Blood concentration: When limaprost was orally administered to 40 healthy adults in fasting condition at a single dose of 5 μg, the plasma concentration reached a maximum of 1.55 pg/mL 0.333 hours after administration and decreased with a half-life of 0.511 hours. (See figure and Table 1.)

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Metabolism: Limaprost was metabolized by undergoing β-oxidation at α-chain, oxidation at the terminal of ω-chain, isomerization of a cyclopentene ring or reduction of a carbonyl group at C-9.
Limaprost did not inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 (in vitro).
Protein binding: The protein binding rate to human plasma at the concentration of 0.023 mM was 95.8% (in vitro, ultrafiltration method).
(Reference) Absorption and excretion in animals (rats): When [11β-3H] limaprost alfadex was orally given to rats, 90 to 95% of the drug was absorbed, and 75 to 80% of the dose was excreted into bile. About 30% of the dose was excreted into urine and about 70% into feces within 72 hours, after circulating enterohepatically.
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