Humalog Clinical Pharmacology - Insulin Lispro

[Insulin Lispro]

CLINICAL PHARMACOLOGY

Antidiabetic Activity--

The primary activity of insulin, including Humalog, is the regulation of glucose metabolism. In addition, all insulins have several anabolic and anti-catabolic actions on many tissues in the body.

In muscle and other tissues (except the brain), insulin causes rapid transport of glucose and amino acids intracellularly, promotes anabolism, and inhibits protein catabolism.

In the liver, insulin promotes the uptake and storage of glucose in the form of glycogen, inhibits gluconeogenesis, and promotes the conversion of excess glucose into fat. Humalog has been shown to be equipotent to human insulin on a molar basis. One unit of Humalog has the same glucose-lowering effect as one unit of human regular insulin, but its effect is more rapid and of shorter duration. The glucose-lowering activity of Humalog and human regular insulin is comparable when administered to normal volunteers by the intravenous route.

Pharmacokinetics-

Absorption and Bioavailability--

Humalog is as bioavailable as human regular insulin, with absolute bioavailability ranging between 55%-77% with doses betweeen 0.1-0.2 U/ kg, inclusive. Studies in normal volunteers and patients with type 1 (insulin-dependent) diabetes demonstrated that Humalog is absorbed faster than human regular insulin (U-100) (Figure 2). In normal volunteers given subcutaneous doses of Humalog ranging from 0.1-0.4 U/ kg, peak serum levels were seen 30-90 minutes after dosing.

When normal volunteers received equivalent doses of human regular insulin, peak insulin levels occurred between 50-120 minutes after dosing. Similar results were seen in patients with type 1 diabetes. The pharmacokinetic profiles of Humalog and human regular insulin are comparable to one another when administered to normal volunteers by the intravenous route.

Humalog was absorbed at a consistently faster rate than human regular insulin in healthy male volunteers given 0.2 U/ kg human regular insulin or Humalog at abdominal, deltoid, or femoral subcutaneous sites, the three sites often used by patients with diabetes. After abdominal administration of Humalog, serum drug levels are higher and the duration of action is slightly shorter than after deltoid or thigh administration (see DOSAGE AND ADMINISTRATION). Humalog has less intra-and inter-patient variability compared to human regular insulin.