How many hours does Glimepiride (a sulfonylurea) take to be eliminated from the body?

Glimepiride Elimination Time from the Body

Glimepiride is eliminated from the body within approximately 24 hours, with a terminal half-life of 5-9 hours in most patients. 1

Pharmacokinetic Profile of Glimepiride

Absorption and Distribution

• Glimepiride reaches peak drug concentrations (Cmax) 2-3 hours after oral administration 1
• When taken with meals, Cmax and AUC are decreased by 8% and 9%, respectively 1
• Protein binding is greater than 99.5% after absorption 1
• Volume of distribution is approximately 8.8 L (113 mL/kg) 1

Metabolism

Glimepiride undergoes complete metabolism through oxidative biotransformation:

• Primary metabolism occurs via Cytochrome P450 2C9, creating the cyclohexyl hydroxy methyl derivative (M1) 1
• M1 is further metabolized to the carboxyl derivative (M2) by cytosolic enzymes 1
• M1 possesses about one-third of the pharmacological activity of glimepiride 1, 2
• The hydroxymetabolite (M1) shows measurable pharmacological activity in humans, with studies showing it can decrease serum glucose concentration by 12% 2

Excretion

• Approximately 60% of glimepiride is recovered in urine within 7 days 1
• M1 and M2 metabolites account for 80-90% of the radioactivity recovered in urine 1
• Approximately 40% of total radioactivity is recovered in feces 1
• No parent drug is recovered from urine or feces, indicating complete metabolism 1

Special Population Considerations

Elderly Patients

• No significant differences in glimepiride pharmacokinetics between patients ≤65 years and >65 years 1
• Mean AUC at steady state for older patients is approximately 13% lower than for younger patients 1
• Mean weight-adjusted clearance for older patients is approximately 11% higher than for younger patients 1

Obesity

• No clinically significant differences in oral clearance of glimepiride between obese and non-obese patients 3
• Obese patients may excrete greater amounts of metabolites M1 and M2 over a 24-hour period 3
• No special dose consideration is required for obese patients with type 2 diabetes 3

Gender and Race

• No differences between males and females in pharmacokinetics when adjusted for body weight 1
• No significant differences in efficacy among Caucasians, Blacks, and Hispanics 1

Clinical Implications

• The greatest blood glucose-lowering effects occur in the first 4 hours after dosing 4
• Glimepiride has linear pharmacokinetics across the 1-8 mg dose range 1
• Intraindividual and interindividual variabilities of pharmacokinetic parameters are 15-23% and 24-29%, respectively 1

Practical Considerations

• Due to its elimination profile, glimepiride is typically administered once daily 4
• Patients with hepatic or renal impairment may require dosage adjustment, although pharmacokinetics are generally not significantly altered 4
• The drug's relatively short half-life allows for convenient once-daily dosing while maintaining efficacy throughout a 24-hour period 4

While the metabolites may be detected for up to 7 days in urine, the active parent compound is effectively eliminated within 24 hours, which aligns with its clinical dosing schedule.