Table 2.

Summary of the pharmacokinetic profile of subcutaneous burosumab in adults with X-linked hypophosphatemia [5, 7, 10, 15]

Parameter	Comments
Absorption	Absorbed slowly (mean tmax 8–11 daysa), with almost 100% bioavailability
Exposure and duration of activity	Dose proportional over the range of 0.1–2.0 mg/kg
	In a population analysis of adults with XLH receiving dose-titrated burosumab every 28 days for 16 months, peak mean serum phosphorus levels progressively ↑ after the first 4 doses, with comparable peak phosphorus levels after doses 6–10, and a slight ↓ thereafter
Pharmacokinetic–pharmacodynamic relationship	Direct relationship; serum concentrations of burosumab and phosphorus ↑ and ↓ in a parallel linear manner, and peak at approximately the same timepoint after each dose
Distribution	Apparent volume of distribution: 8 La (i.e., approximately the volume of plasma in adults with XLH), suggesting limited extravascular distribution
Metabolism	Exact pathway not known; expected to be broken into small peptides and amino acids via catabolic pathways
	Hepatic mechanisms are unlikely to be involved
Elimination	Clearance: low and body-weight dependent; apparent clearance 0.290 and 0.136 L/day in a typical 70-kg adult and 30-kg child with XLH, respectively
	Mean terminal half-life: ≈ 19 daysa
	Excretion: not expected to be directly excreted due to its molecular size

T _max time to maximum serum concentration, XLH X-linked hypophosphatemia, ↑ increase, ↓ decrease

^aIn a typical 70-kg adult with XLH receiving the approved starting dose of burosumab (i.e., 1 mg/kg)