Renal Insufficiency

The metabolism and excretion of glipizide may be slowed in patients with impaired renal function (see PRECAUTIONS).

In patients with decreased renal function (based on creatinine clearance), the plasma and blood half-life of metformin is prolonged and the renal clearance is decreased in proportion to the decrease in creatinine clearance (see Table 1; also, see WARNINGS).

Geriatrics

There is no information on the pharmacokinetics of glipizide in elderly patients. Limited data from controlled pharmacokinetic studies of metformin in healthy elderly subjects suggest that total plasma clearance is decreased, the half-life is prolonged, and Cmax is increased, compared to healthy young subjects. From these data, it appears that the change in metformin pharmacokinetics with aging is primarily accounted for by a change in renal function (see Table 1). Metformin treatment should not be initiated in patients ≥80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced.

Table 1: Select Mean (±S.D.) Metformin Pharmacokinetic Parameters Following Single or Multiple Oral Doses of Metformin Subject Groups: Cmaxb(μg/mL) Tmaxc (hrs)  Renal
MetforminDose a (Number of Subjects)    Clearance (mL/min)
a All doses given fasting except the first 18 doses of the multiple-dose studies 
b Peak plasma concentration 
c Time to peak plasma concentration 
d SD=single dose 
e Combined results (average means) of five studies: mean age 32 years (range 23-59 years) 
f Kinetic study done following dose 19, given fasting 
gElderly subjects, mean age 71 years (range 65-81 years) 
h CLcr=creatinine clearance normalized to body surface area of 1.73 m2
Healthy, Nondiabetic Adults:
500 mg SD d (24)
850 mg SD (74) e
850 mg t.i.d. for 19 doses f (9)
1.03 (±0.33)
1.60 (±0.38)
2.01 (±0.42)
2.75 (±0.81)
2.64 (±0.82)
1.79 (±0.94)
600 (±132)
552 (±139)
642 (±173)
Adults with Type 2 Diabetes:
850 mg SD (23)
850 mg t.i.d. for 19 doses f (9)
1.48 (±0.5)
1.90 (±0.62)
3.32 (±1.08)
2.01 (±1.22)
491 (±138)
550 (±160)
Elderly g, Healthy Nondiabetic
Adults:
850 mg SD (12)

2.45 (±0.70)

2.71 (±1.05)

412 (±98)
Renal-impaired Adults: 850 mg SD
Mild (CLcrh 61-90 mL/min) (5)
Moderate (CLcr 31-60mL/min)(4)
Severe (CLcr 10-30 mL/min) (6)
1.86 (±0.52)
4.12 (±1.83)
3.93 (±0.92)
3.20 (±0.45)
3.75 (±0.50)
4.01 (±1.10)
384 (±122)
108 (±57)
130 (±90)

Pediatrics

No data from pharmacokinetic studies in pediatric subjects are available for glipizide. After administration of a single oral GLUCOPHAGE 500 mg tablet with food, geometric mean metformin Cmax and AUC differed less than 5% between pediatric type 2 diabetic patients (12 to 16 years of age) and gender- and weight-matched healthy adults (20 to 45 years of age), all with normal renal function.

Gender

There is no information on the effect of gender on the pharmacokinetics of glipizide. metformi