Dosing Schedule

With all compounds one should start treatment with the lowest effective dose and titrate upward until sufficient control or a maximal dose is achieved. The drug dose can be increased every 1 to 2 weeks. The first-generation compounds tolbutamide (500-2500 mg), tolazamide (100-1000 mg), and chlorpropamide (100-500 mg) required larger doses to be effective. Glipizide requires 5 to 20 mg, with 20 mg being the maximally effective dose, although doses of up to 40 mg have been approved. Glibenclamide (gliburide in the United States) can be given once daily, or in a divided dose of 1.75 to 10.5 mg for the micronized preparation, or up to 15 mg/day for the conventional, larger particle preparation. Glimepiride is given once daily in doses of 1 to 4 mg. Higher doses (8 mg) have been approved, but do not afford additional effects.

Gliquidon is administered once daily until a dose of 30 mg, higher doses, up to 120 mg, are given in a divided dose twice daily. The dose is also divided for patients with advanced renal impairment. Gliclazide was recently offered in a new once-daily formulation (MR)

TABLE 1 Pharmacokinetic Properties of Sulfonylureas

Sulfonylurea

Enteral resorption

Bioavailability

(%)

(h)

Plasma-protein binding (%)

Placental passage

Dose per day

Onset of effect (min)

Max. effect (h)

Duration of effect (h)

Hepatic metabolism

Excretion by the kidney (%)

Other ways of excretion

Tolbutamide

Fast

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