In healthy subjects, the regadenoson plasma concentration-time profile is multi-exponential in nature and best characterized by 3-compartment model. The maximal plasma concentration of regadenoson is achieved within 1 to 4 minutes after injection of regadenoson and parallels the onset of the pharmacodynamic response. The half-life of this initial phase is approximately 2 to 4 minutes. An intermediate phase follows, with a half-life on average of 30 minutes coinciding with loss of the pharmacodynamic effect. The terminal phase consists of a decline in plasma concentration with a half-life of approximately 2 hours [see Clinical Pharmacology (12.2)]. Within the dose range of 0.3 to 20 mcg/kg in healthy subjects, clearance, terminal half-life or volume of distribution do not appear dependent upon the dose. 

A population pharmacokinetic analysis including data from subjects and patients demonstrated that regadenoson clearance decreases in parallel with a reduction in creatinine clearance and clearance increases with increased body weight. Age, gender, and race have minimal effects on the pharmacokinetics of regadenoson.

Specific Populations

Renally Impaired Patients: The disposition of regadenoson was studied in 18 patients with various degrees of renal function and in 6 healthy subjects. With increasing renal impairment, from mild (CLcr 50 to < 80 mL/min) to moderate (CLcr 30 to < 50 mL/min) to severe renal impairment (CLcr < 30 mL/min), the fraction of regadenoson excreted unchanged in urine and the renal clearance decreased, resulting in increased elimination half-lives and AUC values compared to healthy subjects (CLcr ≥ 80 mL/min). However, the maximum observed plasma concentrations as well as volumes of distribution estimates were similar across the groups. The plasma concentration-time profiles were not significantly altered in the early stages after dosing when most pharmacologic effects are observed. No dose adjustment is needed in patients with renal impairment. 

Patients with End Stage Renal Disease: The pharmacokinetics of regadenoson in patients on dialysis has not been assessed; however, in an in vitro study regadenoson was found to be dialyzable.

Hepatically Impaired Patients: The influence of hepatic impairment on the pharmacokinetics of regadenoson has not been evaluated. Because greater than 55% of the dose is excreted in the urine as unchanged drug and factors that decrease clearance do not affect the plasma concentration in the early stages after dosing when clinically meaningful pharmacologic effects are observed, no dose adjustment is needed in patients with hepatic impairment.

Geriatric Patients: Based on a population pharmacokinetic analysis, age has a minor influence on the pharmacokinetics of regadenoson. No dose adjustment is needed in elderly patients.

Metabolism

The metabolism of regadenoson is unknown in humans. Incubation with rat, dog, and human liver microsomes as well as human hepatocytes produced no detectable metabolites of regadenoson. 

Excretion

In healthy volunteers, 57% of the regadenoson dose is excreted unchanged in the urine (range 19 to 77%), with an average plasma renal clearance around 450 mL/min, i.e., in excess of the glomerular filtration rate. This indicates that renal tubular secretion plays a role in regadenoson elimination.