PRODUCT MONOGRAPH IMITREX DF IMITREX ... - GlaxoSmithKline

PharmacokineticsPharmacokinetic parameters following subcutaneous, oral or intranasal administration areshown in Table 5.Inter-patient and intra-patient variability was noted in most pharmacokinetic parametersassessed.Table 5Summary of Pharmacokinetic ParametersParameter Subcutaneous Oral IntranasalBioavailability 96% 14% 16%C max (ng/mL) 6 mg: 72 ng/mL 100 mg:50-60ng/mL25 mg: 18 ng/mL5 mg: 4.7 ng/mL10 mg: 8.5 ng/mL20 mg: 14.4 ng/mLTmax 6 mg: 15min 100 mg: 0.5-5 hr* 1-1.5 hrT ½ 2 hr (1.7-2.3 hr) 2 hr (1.9-2.2hr) 2hr (1.3-5.4hr)Protein Binding 14-21%Volume of Distribution170 LTotal Plasma Clearance1160 mL/minRenal Plasma Clearance260 mL/min* 70% to 80% of C max values were attained within 30-45 minutes of dosing.Absorption/Metabolism: Sumatriptan is rapidly absorbed after oral, subcutaneous andintranasal administration. The low oral and intranasal bioavailability is primarily due tometabolism (hepatic and pre-systemic) and partly due to incomplete absorption. The oralabsorption of sumatriptan is not significantly affected either during migraine attacks or byfood.In vitro studies with human microsomes suggest that sumatriptan is metabolized bymonoamine oxidase (MAO), predominantly the A isoenzyme. In studies conducted in alimited number of patients, MAO inhibitors reduce sumatriptan clearance, significantlyincreasing systemic exposure.Excretion: Non-renal clearance of sumatriptan accounts for about 80% of the totalclearance. The major metabolite, the indole acetic acid analogue of sumatriptan, ismainly excreted in the urine where it is present as a free acid (35%) and the glucuronideconjugate (11%). It has no known 5-HT 1 or 5-HT 2 activity. Minor metabolites have notbeen identified.Special Populations and ConditionsGeriatrics: No differences have been observed between the pharmacokinetic parametersin healthy elderly volunteers and those in younger volunteers (less than 65 years old).October 21, 2014Page 22 of 58