From the Guidelines
Linagliptin is a DPP-4 inhibitor that can be dosed at 5 mg once daily in patients with impaired renal function, including those with end-stage renal disease, without requiring any dose adjustment. The pharmacokinetic properties of linagliptin include a maximum plasma concentration (Cmax) of approximately 8-10 nmol/L within 1.5 to 2 hours (Tmax) after oral administration 1.
Key Pharmacokinetic Properties
- High protein binding (primarily to DPP-4 enzyme itself)
- Large apparent volume of distribution
- Nonlinear pharmacokinetics due to concentration-dependent binding to DPP-4
- Minimal renal elimination (less than 5%)
- Approximately 80% eliminated through the enterohepatic system and fecal excretion
- Terminal half-life of about 100 hours, contributing to its sustained effect with once-daily dosing
Dosing in Impaired Renal Function
According to the most recent guidelines, linagliptin does not require dose adjustment in patients with impaired renal function, including those with end-stage renal disease 1.
Comparison with Other DPP-4 Inhibitors
In contrast to other DPP-4 inhibitors such as sitagliptin, saxagliptin, and alogliptin, which require dose adjustments in patients with renal dysfunction, linagliptin's unique pharmacokinetic profile makes it a valuable option for diabetic patients with kidney disease 1. Some key points to consider when prescribing linagliptin include:
- No dose adjustment is necessary in patients with liver or renal insufficiency
- Linagliptin can be used in combination with other medications, such as metformin, to achieve better glycemic control
- The drug has a neutral or mild effect on weight gain and does not increase the risk of hypoglycemia when used alone 1.
From the FDA Drug Label
The absolute bioavailability of linagliptin is approximately 30% A high-fat meal reduced Cmax by 15% and increased AUC by 4%; this effect is not clinically relevant. Plasma AUC of linagliptin increased in a less than dose-proportional manner in the dose range of 1 to 10 mg. In patients with moderate renal impairment under steady-state conditions, mean exposure of linagliptin increased (AUCτ,ss by 71% and Cmax by 46%) compared with healthy subjects. Patients with type 2 diabetes mellitus and severe renal impairment showed steady-state exposure approximately 40% higher than that of patients with type 2 diabetes mellitus and normal renal function (increase in AUCτ,ss by 42% and Cmax by 35%)
The pharmacokinetic properties of Linagliptin include:
- Cmax: reduced by 15% with a high-fat meal, increased by 46% in patients with moderate renal impairment, and increased by 35% in patients with severe renal impairment
- Tmax: not explicitly stated in the provided text
- Dosing in patients with impaired renal function:
- Patients with mild renal impairment: comparable exposure to healthy subjects
- Patients with moderate renal impairment: increased exposure (AUCτ,ss by 71% and Cmax by 46%) compared to healthy subjects
- Patients with severe renal impairment: approximately 40% higher exposure than patients with normal renal function 2
From the Research
Pharmacokinetic Properties of Linagliptin
- Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that is eliminated predominantly via a nonrenal route 3, 4, 5.
- The pharmacokinetic profile of linagliptin is characterized by a high selectivity and potency for DPP-4 inhibition, with ≥ 80% inhibition of DPP-4 throughout the 24-hour dosing interval 6.
- Linagliptin has a dose-dependent inhibition of DPP-4, and its efficacy in improving glycaemic control has been demonstrated in several clinical trials 3, 4, 6.
C max and T max of Linagliptin
- The maximum concentration (C max) and time to reach maximum concentration (T max) of linagliptin are not explicitly stated in the provided studies.
- However, it is mentioned that linagliptin 5 mg once daily has been shown to be clinically effective and well tolerated in patients with type 2 diabetes mellitus 3, 4, 5.
Dosing in Patients with Impaired Renal Function
- Linagliptin can be used without dosage adjustment in patients with renal impairment of any degree, as it is eliminated primarily via a nonrenal route 3, 4, 5.
- This is in contrast to other DPP-4 inhibitors, which may require dosage adjustment in patients with renal impairment.
- The efficacy and safety of linagliptin in patients with renal impairment have been demonstrated in several clinical trials, including those with severe renal impairment 4, 5.