glutide following subcutaneous administration is approximately 55%.
Distribution - The mean apparent volume of distribution after subcutaneous administration of Victoza 0.6 mg is approximately 13 L. The mean volume of distribution after intravenous administration of Victoza is 0.07 L/kg. Liraglutide is extensively bound to plasma protein (>98%).
Metabolism - During the initial 24 hours following administration of a single [3H]-liraglutide dose to healthy subjects, the major component in plasma was intact liraglutide. Liraglutide is endogenously metabolized in a similar manner to large proteins without a specific organ as a major route of elimination.
Elimination - Following a [3H]-liraglutide dose, intact liraglutide was not detected in urine or feces. Only a minor part of the administered radioactivity was excreted as liraglutide-related metabolites in urine or feces (6% and 5%, respectively). The majority of urine and feces radioactivity was excreted during the first 6-8 days. The mean apparent clearance following subcutaneous administration of a single dose of liraglutide is approximately 1.2 L/h with an elimination half-life of approximately 13 hours, making Victoza suitable for once daily administration.
Special PopulationsElderly - Age had no effect on the pharmacokinetics of Victoza based on a pharmacokinetic study in healthy elderly subjects (65 to 83 years) and population pharmacokinetic analyses of patients 18 to 80 years of age [see Use in Specific Populations (8.5)].
Gender - Based on the results of population pharmacokinetic analyses, females have 34% lower weight-adjusted clearance of Victoza compared to males. Based on the exposure response data, no dose adjustment is necessary based on gender
Race and Ethnicity - Race and ethnicity had no effect on the pharmacokinetics of Victoza based on the results of population pharmacokinetic analyses that included Caucasian, Black, Asian and Hispanic/Non-Hispanic subjects.
Body Weight - Body weight significantly affects the pharmacokinetics of Victoza based on results of population pharmacokinetic analyses. The exposure of liraglutide decreases with an increase in baseline body weight. However, the 1.2 mg and 1.8 mg daily doses of Victoza provided adequate systemic exposures over the body weight range of 40 – 160 kg eva luated in the clinical trials. Liraglutide was not studied in patients with body weight >160 kg.
Pediatric - Victoza has not been studied in pediatric patients [see Use in Specific Populations (8.4)].
Renal Impairment - The single-dose pharmacokinetics of Victoza were eva luated in subjects with varying degrees of renal impairment. Subjects with mild (estimated creatinine clearance 50-80 mL/min) to severe (estimated creatinine clearance <30 mL/min) renal impairment and subjects with end-stage renal disease requiring dialysis were included in the trial. Compared to healthy subjects, liraglutide AUC in mild, moderate, and severe renal impairment and in end-stage renal disease was on average 35%, 19%, 29% and 30% lower, respectively [see Use in Specific Populations (8.6)].
Hepatic Impairment - The single-dose pharmacokinetics of Victoza were eva luated in subjects with varying degrees of hepatic impairment. Subjects with mild (Child Pugh score 5-6) to severe (Child Pugh score > 9) hepatic impairment were included in the trial. Compared to healthy subjects, liraglutide AUC in subjects with mild, moderate and severe hepatic impairment was on aver |
