The primary pharmacologic effect of IGF-1 in children is the promotion of linear growth. Secondary pharmacologic actions of IGF-1 include other anabolic effects, insulin sensitization, and insulin-like effects. There are no known direct growth-promoting effects of IGFBP-3. The primary effect of IGFBP-3 in the mecasermin rinfabate complex is the modulation of IGF-1 action.

In normal human circulation, less than 2% of total IGF-1 exists in the free form. Most circulating IGF-1 is found in association with the growth hormone (GH)-dependent binding protein IGFBP-3, and this binary complex further associates with a third serum protein, the GH-dependent acid-labile subunit (ALS), to form a non-covalent ternary complex of ~150 kD, which represents the natural physiologic reservoir of IGF-1. The ternary complex consists of one molecule each of IGF-1, IGFBP-3, and ALS.

The half-life of IGF-1 in the ternary complex is >12 hr. Proteolytic cleavage of IGFBP-3 and interaction of the ternary complex with proteoglycans have been shown to release IGF-1 from the ternary complex.

In pediatric patients with severe primary IGF-1 deficiency (Primary IGFD), 1 mg/kg was administered by subcutaneous injection to 4 patients in a pharmacokinetic sub-study of the clinical trial. A summary of the pharmacokinetic parameters for IGF-1 and IGFBP-3, uncorrected for baseline values, is presented in Table 1 and Figure 1. The assays employed do not distinguish between exogenous and endogenous IGF-1 or IGFBP-3.

Figure 1. Mean (±SD) Uncorrected IGF-1 (Panel A) and IGFBP-3 (Panel B) (ng/mL) Concentrations in Patients with Primary IGFD Treated with IPLEX^® 1 mg/kg (n=4)

Special Populations

Geriatric: The pharmacokinetics of IPLEX^® have not been studied in subjects greater than 65 years of age.

Gender: No information is available.

Race: No information is available.

Renal insufficiency: No studies have been conducted to determine the effect of renal impairment on the pharmacokinetics of IPLEX^®.

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