Considerations for pharmacokinetic assessment of immunoglobulins: Gammagard in very low birth weight neonates with and without baseline-correction.

BACKGROUND

Immunoglobulins are widely used across multiple therapeutic areas such as immunodeficiency syndromes, infection and autoimmune diseases. The pharmacokinetics (PK) of immunoglobulins are well characterized in adults, but very little is known about the PK of immunoglobulins in neonates and infants.

OBJECTIVE

The objective of the present study was to characterize the PK of Gammagard, an immunoglobulin, in very low birth weight preterm neonates.

METHOD

Gammagard concentration-time data from very low birth weight neonates (bodyweight range 0.78-1.38 kg, n = 20) following intravenous administration of 500 mg/kg and 750 mg/kg were obtained from the literature. The data were analyzed with and without baseline correction using extensive blood samples (8 blood samples). Model-independent (non-compartmental) analysis was used to characterize the PK of Gammagard.

RESULTS

Based on uncorrected baseline concentration-time data, the clearance and half-life of Gammagard were 3.1 ± 0.7 mL/day and 22 ± 6 days, respectively. Based on corrected baseline concentration-time data, the clearance and half-life of Gammagard were 20.2 ± 7.4 mL/day and 5.3 ± 2.2 days, respectively.

CONCLUSION

The dose of immunoglobulins should be adjusted based on the PK of baseline corrected rather than baseline uncorrected profiles because baseline corrected PK parameters especially half-life reconciles with PK principles.