Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

12.2 Pharmacodynamics
Following SC administration in XLH patients, higher burosumab concentrations were associated with greater increase of serum phosphorus levels. The increase in serum phosphorus was reversible and returned to baseline with elimination of systemic burosumab.
Ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) showed dose-dependent increases from baseline [see Clinical Studies (14)].
Elevation in serum total FGF23 was observed after initiation of burosumab treatment, however, the clinical implication is unknown.

Pharmacokinetic Properties

12.3 Pharmacokinetics
The following pharmacokinetic parameters were observed in patients with XLH administered the approved recommended starting dosage based on a 70 kg patient, unless otherwise specified. Based on the population PK analysis, the PK characteristics of burosumab were similar between patients with XLH and TIO.

Burosumab exhibited linear pharmacokinetics following SC injections within the dose range of 0.1 to 1 mg/kg (0.08 to 0.8 times the maximum approved recommended dosage based on a 70 kg patient with XLH).
The steady-state trough mean (± SD) concentration of burosumab was 5.8 (± 3.4) mcg/mL in adult XLH patients.
Absorption
The burosumab mean Tmax values ranged from 8 to 11 days.
Distribution
The apparent volume of distribution of burosumab is 8 L.
Elimination
The apparent clearance is 0.290 L/day. The half-life of burosumab is approximately 19 days.
Metabolism
The exact pathway for burosumab metabolism has not been characterized. Burosumab is expected to be degraded into small peptides and amino acids via catabolic pathways.
Specific Populations
No clinical significant difference in burosumab pharmacokinetics was observed based on age.
The effect of renal or hepatic impairment on the pharmacokinetics of burosumab is unknown.
Pediatric Patients
The steady-state trough concentration was 15.8 (± 9.4) mcg/mL in patients aged 5-12 years, and 11.2 (± 4.6) mcg/mL in XLH patients aged 1-4 years.
Body Weight
Clearance and volume of distribution of burosumab increases with body weight.
Drug Interaction Studies
No drug interaction studies have been conducted with CRYSVITA.