| |
|
Pharmacokinetics |
|
Recommended Dosages |
| |
|
Onset
(i=initial)
(p=peak) |
|
Duration
of action |
|
Metabolism |
|
Active
metabolites |
|
Approved normal daily dose |
|
Dosage Adjustment for Special Populations |
| First generation sulphonylureas
|
| Chlorpropamide |
|
~ 2hrs(i)
3-6 hrs(p) |
|
>48hrs |
|
Liver |
|
N |
|
100-500mg once daily |
|
E: |
initial: 100-125mg/day |
| RF: |
Y |
| Hi: |
Conservative initial and maintenance dose |
| Tolbutamide |
|
1 hr(i)
5-8hrs(p) |
|
12 hrs |
|
Liver |
|
N |
|
500-3000mg/day
(in divided doses) |
|
E: |
N |
| RF: |
N |
| Hi: |
Y |
| Second generation sulphonylureas |
| Glibenclamide |
|
30mins(i)
2-3 hrs(p) |
|
24 hrs |
|
Liver |
|
Y |
|
1.25-20mg/day
(once or BD) |
|
E: |
Conservative initial and maintenance dose |
| RF: |
Y (avoid if CrCl < 50ml/min) |
| Hi: |
Conservative initial and maintenance dose |
| Gliclazide |
|
4-5hrs(p) |
|
24 hrs |
|
Liver |
|
N |
|
iR:40-320mg/day
(once or divided
doses)
MR: 30-120mg once daily |
|
E: |
N |
| RF: |
Y (avoid in severe case) |
| Hi: |
Y |
| Glipizide |
|
30 mins(i) |
|
24 hrs |
|
Liver |
|
N |
|
2.5-40mg/day
(once or divided doses)
( 30mins before food) |
|
E: |
Start with low dose, 2.5mg/day 2-3 hrs(p) |
| RF: |
N (some investigators suggested to avoid if CrCl<10ml/min)
|
| Hi: |
Start with low dose, 2.5mg/day |
| Glimepiride |
|
2-3hrs(p) |
|
24 hrs |
|
Liver |
|
Y |
|
1-8mg once daily |
|
E: |
Start with low dose (1mg daily) |
| RF: |
Start with low dose (1mg daily) |
| Hi: |
Start with low dose (1mg daily) (avoid in severe
case) |
| Meglitinides |
| Nateglinide |
|
~20mins(i)
1hrs(p) |
|
4 hrs |
|
Liver |
|
Y |
|
60-120mg tds
(30 mins to immediately before meals) |
|
E: |
N |
| RF: |
N |
| Hi: |
Not necessary for mild hepatic insufficiency |
| Repaglinide |
|
~15-60mins(i)
~1 hr(p) |
|
4-6 hrs |
|
Liver |
|
N |
|
0.5-4 mg
(30 mins to immediately before meals)
Max: 16mg/day |
|
E: |
N |
| RF: |
0.5mg before meals in severe renal impairment |
| Hi: |
Use cautiously in hepatic insufficiency (use longer
dosage interval) |
| Alpha-glucosidase inhibitors |
| Acarbose |
|
1 hr(p) |
|
8-12 hrs |
|
intestinal wall |
|
Y |
|
50-100mg tds before each main |
|
E: |
ND meal |
| RF: |
ND |
| Hi: |
Contraindicated in cirrhosis |
| BiguanidesMetformin |
|
Within days(i)
2 weeks(p) |
|
12-24 hrs |
|
None |
|
N |
|
500mg-2550mg/day in divided |
|
E: |
Start with conservative dose doses |
| RF: |
Contraindicated (increase risk of lactic acidosis,
avoided if CrCl<60-70ml/min) |
| Hi: |
Not recommended |
| Thiazolidinediones |
|
|
|
|
|
|
|
|
|
|
|
|
|
| Pioglitazone |
|
several weeks(p) |
|
4 weeks (multiple dose) |
|
Liver |
|
Y |
|
15-45mg once daily without regards to
meals
(if used as monotherapy) |
|
E: |
N |
| RF: |
N |
| Hi: |
Not to be used in patients with active liver disease
or with serum transaminase levels (ALT) exceed 2.5 times the
upper limit of normal. |
| Rosiglitazone |
|
Onset of action
is delayed
12 weeks(p) |
|
ND |
|
Liver |
|
ND |
|
4mg - 8mg daily
(once or divided twice daily)
without regards to meals
(reduced if in concurrent use with insulin) |
|
E: |
N |
| Ri: |
N |
| Hi: |
Not to be used in patients with active liver disease
or with serum transaminase levels (ALT) exceed 2.5 times the
upper limit of normal. |
| E = Elderly, RF = Renal failure, Hi
= Hepatic insufficiency, N = No, Y= Yes, ND = Data not available,
CrCl = Creatinine clearance, iR = immediate release formulation,
MR = Modified release formulation |