Ibudilast

Ibudilast belongs to the pharmacological class Non-Xanthine PDE₄ Inhibitor

Ibudilast has been approved for relieving symptoms and also for the treatment and maintenance of episodes of asthma, multiple sclerosis, and cerebrovascular disease.

The common side effects associated with Ibudilast are redness of eye and skin, nausea, diarrhea, and dyspepsia.

Ibudilast is available in the form of tablets, mainly available in Japan.

Ibudilast belongs to the pharmacological class Non-Xanthine PDE₄ Inhibitor

Ibudilast reduces the symptoms associated with conditions such as episodes of asthma, multiple sclerosis, and cerebrovascular disease.

Ibudilast is available in tablets and should be swallowed whole with water.

Ibudilast can be used in the treatment of:

• Multiple Sclerosis
• Asthma
• Cerebrovascular Disease

Ibudilast can help to relieve symptoms and also for the treatment and maintenance of episodes of asthma, multiple sclerosis, and cerebrovascular disease.

Ibudilast is approved for use in the following clinical indications:

• Multiple Sclerosis
• Asthma
• Cerebrovascular Disease

Ibudilast can be administered orally before/ after meals. The dosage and duration of treatment should be as per the clinical judgment of the treating physician.

60mg/day

Tablet

The common side effects of Ibudilast include the following:

• Nausea
• Diarrhea
• Dyspepsia

The physician should be knowledgeable and vigilant about the treatment pertaining to the identification and treatment of overdosage of Ibudilast.

Basic Pharmacology

Ibudilast is a pyrazolo-pyridine small molecule that is a relatively non-selective phosphodiesterase (PDE) inhibitor. It inhibits human PDEs 3,4,10, and 11 with IC50s ranging from approximately 1-10 µM. Given the modest but proven efficacy of PDE4 inhibitors in asthma, there is a rationale for using this compound in asthma. In guinea pigs, ibudilast 1-4 mg/kg iv attenuated ovalbumin challenge and leukotriene D4- induced airway constriction.

Pharmacokinetics:

The pharmacokinetics of ibudilast were previously examined after a single 30 mg dose and after multiple doses of 30 mg twice daily for 14 days in nine healthy men and nine healthy Caucasian women. A commercial modified release formulation (Pinatos) was used in this, and the studies are described below. Peak plasma concentrations after the single dose were 32 ng/ml, reached at a median of five hours. The apparent elimination half-life was 19 hours. Steady-state was reached by day two. The negligible drug was eliminated in the urine. These results corroborate well with earlier studies in Japanese at lower doses, although dose-adjusted exposure in Japanese was slightly higher.

Single-dose pharmacokinetics were linear over a higher dose range from 30-100 mg in healthy male and female volunteers. Absorption was non-significantly increased by approximately 10% with a high-fat meal. Apparent clearance when fasted was approximately 650 ml/min. In a two-week repeat dose study comparing the tolerability and pharmacokinetics of ibudilast 20-50 mg bid in 12 healthy subjects and 12 diabetics, it was generally well tolerated in both populations, albeit with somewhat increased GI side effects in the diabetic subjects. No significant differences were found in ibudilast pharmacokinetics between the groups and were, furthermore, comparable with other studies. However, the diabetics had slightly lower circulating levels of the 6,7–dihydrodiol metabolite and corresponding slightly higher plasma ibudilast levels. Ibudilast pharmacokinetics have generally been dose-proportional in single administration or repeat dose trials. Interestingly, while plasma ibudilast levels in multi-day repeat dosing studies in rats display significant diminution within 1-2 weeks, steady-state drug levels remain stable in humans for at least two weeks of repeat dosing. Ibudilast is negligibly excreted in urine as an unchanged drug. A major metabolite, 6, 7 – dihydrodiol ibudilast, was detected in plasma, at concentrations averaging 30-40% of the parent. Low levels of monohydroxylated metabolite and glucuronides of the mono and dihydro metabolites were detected in urine.

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