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How pharmacokinetic and pharmacodynamic principles pave the way for optimal basal insulin therapy in type 2 diabetes.

Arnolds S, Kuglin B, Kapitza C, Heise T - Int. J. Clin. Pract. (2010)

Bottom Line: The main conclusion is that PD parameters are of greater clinical significance for insulin therapy than PK parameters.The review further explains how PD parameters have been translated into useful clinical concepts and simple titration algorithms for everyday clinical practice.Finally, the necessity of overcoming patient and/or physician barriers to insulin therapy and providing continuing education and training is emphasised.

View Article: PubMed Central - PubMed

Affiliation: PROFIL Institut für Stoffwechselforschung GmbH, Neuss, Germany. sabine.arnolds@profil-research.de

ABSTRACT
This pedagogical review illustrates the differences between pharmacokinetic (PK) and pharmacodynamic (PD) measures, using insulin therapy as the primary example. The main conclusion is that PD parameters are of greater clinical significance for insulin therapy than PK parameters. The glucose-clamp technique, the optimal method for determining insulin PD, is explained so that the reader can understand the important studies in the literature. Key glucose-clamp studies that compare two basal insulin analogues - insulin glargine and insulin detemir - to Neutral Protamine Hagedorn insulin and to each other are then presented. The review further explains how PD parameters have been translated into useful clinical concepts and simple titration algorithms for everyday clinical practice. Finally, the necessity of overcoming patient and/or physician barriers to insulin therapy and providing continuing education and training is emphasised.

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Glucose infusion rates in glucose-clamp experiments on rapid-acting insulins (64)
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fig04: Glucose infusion rates in glucose-clamp experiments on rapid-acting insulins (64)

Mentions: A number of parameters of interest can be derived from PD profiles (Figure 3). These include the area under the curve (AUC), i.e., the overall glucose-lowering effect/glucose disposal, and GIRmax and tmax, i.e., the magnitude and time of peak effect, respectively. Also relevant to patients are the time to 50% of maximum effect (early t50%), i.e., the onset of action of the respective insulin, and the time when the maximum effect has fallen again by 50% (late t50%), i.e., the vanishing effect/end of action. For basal insulins, important parameters include: duration of action, i.e., the time period between insulin injection and end of action; and the end of action, i.e., the time from injection of the study insulin to an increase in serum glucose concentration above a predetermined value (often 8.3 mmol/l) (13). The duration of action can only be measured reliably in people with type 1 diabetes. In such patients, a declining metabolic effect of the study insulin causes an immediate rise in blood glucose. By contrast, in healthy people or patients with type 2 diabetes, duration of action can be overestimated because of endogenous insulin secretion. Duration of action is of relevance in patients who are deciding whether to inject basal insulin once- or twice-daily. Figures 4 and 5 provide GIR curves on rapid-acting and long-acting insulins.


How pharmacokinetic and pharmacodynamic principles pave the way for optimal basal insulin therapy in type 2 diabetes.

Arnolds S, Kuglin B, Kapitza C, Heise T - Int. J. Clin. Pract. (2010)

Glucose infusion rates in glucose-clamp experiments on rapid-acting insulins (64)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2984539&req=5

fig04: Glucose infusion rates in glucose-clamp experiments on rapid-acting insulins (64)
Mentions: A number of parameters of interest can be derived from PD profiles (Figure 3). These include the area under the curve (AUC), i.e., the overall glucose-lowering effect/glucose disposal, and GIRmax and tmax, i.e., the magnitude and time of peak effect, respectively. Also relevant to patients are the time to 50% of maximum effect (early t50%), i.e., the onset of action of the respective insulin, and the time when the maximum effect has fallen again by 50% (late t50%), i.e., the vanishing effect/end of action. For basal insulins, important parameters include: duration of action, i.e., the time period between insulin injection and end of action; and the end of action, i.e., the time from injection of the study insulin to an increase in serum glucose concentration above a predetermined value (often 8.3 mmol/l) (13). The duration of action can only be measured reliably in people with type 1 diabetes. In such patients, a declining metabolic effect of the study insulin causes an immediate rise in blood glucose. By contrast, in healthy people or patients with type 2 diabetes, duration of action can be overestimated because of endogenous insulin secretion. Duration of action is of relevance in patients who are deciding whether to inject basal insulin once- or twice-daily. Figures 4 and 5 provide GIR curves on rapid-acting and long-acting insulins.

Bottom Line: The main conclusion is that PD parameters are of greater clinical significance for insulin therapy than PK parameters.The review further explains how PD parameters have been translated into useful clinical concepts and simple titration algorithms for everyday clinical practice.Finally, the necessity of overcoming patient and/or physician barriers to insulin therapy and providing continuing education and training is emphasised.

View Article: PubMed Central - PubMed

Affiliation: PROFIL Institut für Stoffwechselforschung GmbH, Neuss, Germany. sabine.arnolds@profil-research.de

ABSTRACT
This pedagogical review illustrates the differences between pharmacokinetic (PK) and pharmacodynamic (PD) measures, using insulin therapy as the primary example. The main conclusion is that PD parameters are of greater clinical significance for insulin therapy than PK parameters. The glucose-clamp technique, the optimal method for determining insulin PD, is explained so that the reader can understand the important studies in the literature. Key glucose-clamp studies that compare two basal insulin analogues - insulin glargine and insulin detemir - to Neutral Protamine Hagedorn insulin and to each other are then presented. The review further explains how PD parameters have been translated into useful clinical concepts and simple titration algorithms for everyday clinical practice. Finally, the necessity of overcoming patient and/or physician barriers to insulin therapy and providing continuing education and training is emphasised.

Show MeSH