Selected studies that evaluated subcutaneous absorption of protein therapeutics using population analysis (excluding monoclonal antibodies and Fc-fusion proteins)
| Drug | Species/Population | Absorption Model | Absorption Parameters | Between Subject Variability for Absorption Parameters, CV% | Covariates for Absorption Parameters | Reference |
|---|---|---|---|---|---|---|
| Anakinra | Rats | Sequential zero- and first-order | Fraction of zero-order | Yes for ka | No | Liu et al., 2011 |
| Duration of zero-order | ||||||
| ka | ||||||
| Darbepoetin alfa | Anemic patients with chronic kidney disease | Zero-order input into the depot compartment followed by the first-order absorption | F | Yes | No | Doshi et al., 2010 |
| Duration of input | ||||||
| ka | ||||||
| Darbepoetin alfa | Healthy humans | First-order | ka | Yes for ka | F linear function of the dose | Agoram et al., 2007 |
| ka ∝ (Age/50)−0.951 | ||||||
| Erythropoietin δ | Pediatric patients with chronic kidney disease | First-order | F | No | No | Knebel et al., 2008 |
| ka | ||||||
| Erythropoietin | Healthy humans (meta-analysis) | (1) Zero-order input into the depot compartment followed by the first-order absorption | F-hyperbolic function of the dose; | Yes for ka, D1, Tlag, fraction of (1) | ka decreased with age and body weight; | Olsson-Gisleskog et al., 2007 |
| (2) Zero-order after a lag timea | Fraction of (1), dose dependent; | ka lower in females | ||||
| For (1): ka, Duration of zero-order (D1) | F increased with increase in hemoglobin; | |||||
| For (2): Duration of zero-order (D2), Tlag | F decreased with body weight | |||||
| Filgrastim | Healthy adults | Parallel zero- and first-order followed by first-order | F | No | No | Wiczling et al., 2009 |
| Fraction of zero-order | ||||||
| Duration of zero-order | ||||||
| ka | ||||||
| Filgrastim | Healthy adults | First-order | F | No | No | Krzyzanski et al., 2010 |
| ka | ||||||
| Growth hormone | Healthy humans and dialysis patients | Michaelis-Menten | Vmax | No | Km population specific | Klitgaard et al., 2009 |
| Km | ||||||
| Insulin | Healthy humans | First-order with a transit compartment | F | Yes | ka ∝ BMI | Potocka et al., 2011 |
| ka1 | ||||||
| ka2 | ||||||
| Insulin | Rats | Parallel zero- and first-order | Fraction of zero-order | No | No | Gopalakrishnan et al., 2005 |
| Duration of zero-order | ||||||
| Tlag for zero-order | ||||||
| ka | ||||||
| F - dose-dependent function | ||||||
| IFN-α2b | Human hepatitis C patients | Sequential zero- and first-order | Fraction of zero-order | Yes | No | Chatelut et al., 1999 |
| Duration of zero-order | ||||||
| ka | ||||||
| Leukemia inhibitory factor | Healthy postmenopausal women and infertile patients | Zero-order | Duration of zero-order | No | No | Goggin et al., 2004 |
| Low molecular weight heparin | Healthy humans | Parallel zero- and first-order followed by first-order | Fraction of zero-order | Yes for ka and fraction of zero-order | No | Abe et al., 2013 |
| Duration of zero-order | ||||||
| Tlag for zero-order | ||||||
| ka | ||||||
| Pegylated human erythropoietin | Rats, dogs, and monkeys | First-order | F | Yes for ka, F | ka ∝ BW−0.149 | Jolling et al., 2005 |
| ka | Tlag ∝ BW−1.810 | |||||
| Tlag | F – species specific | |||||
| Peginesatide | Chronic kidney disease patients | First-order | F | Yes | ka ∝ BMI, creatinine, ethnicity, dialysis status | Naik et al., 2013 |
| ka |
BMI, body mass index.
↵a The estimated parameters values allowed for two processes to occur simultaneously (D1 = 0.725 h, D2 = 37.8 h, Tlag = 2.72 h) (Olsson-Gisleskog et al., 2007).