Simvastatin

Following an oral dose of 14C-labeled simvastatin in man, 13% of the dose was excreted in urine and 60% in feces. Plasma concentrations of total radioactivity (simvastatin plus 14C-metabolites) peaked at 4 hours and declined rapidly to about 10% of peak by 12 hours postdose.

Special Populations

Renal Impairment

Sitagliptin

A single-dose, open-label study was conducted to eva luate the pharmacokinetics of sitagliptin (50 mg dose) in patients with varying degrees of chronic renal impairment compared to normal healthy control subjects. The study included patients with renal impairment classified on the basis of creatinine clearance as mild (50 to <80 mL/min), moderate (30 to <50 mL/min), and severe (<30 mL/min), as well as patients with ESRD on hemodialysis. In addition, the effects of renal impairment on sitagliptin pharmacokinetics in patients with type 2 diabetes and mild or moderate renal impairment were assessed using population pharmacokinetic analyses. Creatinine clearance was measured by 24-hour urinary creatinine clearance measurements or estimated from serum creatinine based on the Cockcroft-Gault formula:

 CrCl =  [140 - age (years)] × weight (kg) {× 0.85 for female patients}
[72 × serum creatinine (mg/dL)]

Compared to normal healthy control subjects, an approximate 1.1- to 1.6-fold increase in plasma AUC of sitagliptin was observed in patients with mild renal impairment. Because increases of this magnitude are not clinically relevant, dosage adjustment in patients with mild renal impairment is not necessary. Plasma AUC levels of sitagliptin were increased approximately 2-fold and 4-fold in patients with moderate renal impairment and in patients with severe renal impairment, including patients with ESRD on hemodialysis, respectively. To achieve plasma concentrations of sitagliptin similar to those in patients with normal renal function, a lower dosage is recommended in patients with moderate renal impairment. JUVISYNC should not be used in patients with severe renal impairment. [See Dosage and Administration (2.2); Warnings and Precautions (5.4).]

Hepatic Impairment

Sitagliptin

In patients with moderate hepatic impairment (Child-Pugh score 7 to 9), mean AUC and Cmax of sitagliptin increased approximately 21% and 13%, respectively, compared to healthy matched controls following administration of a single 100 mg dose of sitagliptin. These differences are not considered to be clinically meaningful.

There is no clinical experience in patients with severe hepatic impairment (Child-Pugh score >9).

Body Mass Index (BMI)

Sitagliptin

Body mass index had no clinically meaningful effect on the pharmacokinetics of sitagliptin based on a composite analysis of Phase I pharmacokinetic data and on a population pharmacokinetic analysis of Phase I and Phase II data.

Gender

Sitagliptin

Gender had no clinically meaningful effect on the pharmacokinetics of sitagliptin based on a composite analysis of Phase I pharmacokinetic data and on a population pharmacokinetic analysis of Phase I and Phase II data.

Geriatric

Sitagliptin

When the effects of age on renal function are taken into account, age alone did not have a clinically meaningful impact on the pharmacokinetics of sitagliptin based on a population pharmacokinetic ana