Table 2.
Summary of protein pharmacokinetics expressed in terms of the lumped physiological parameters of Figure 1B: plasma metabolic clearance Clp, filtration fractions f1, f2, and lymph flows L1 L2. All results are scaled to a 70 kg human using an assumed plasma volume Vp = 2800 ml. For each species, the 4 parameters L1, L2, V1 and V2 are adjusted as described and assumed constant for all proteins studied in that species. Only 2 parameters are adjusted for each protein: ClP and f ≈f1≈f2. For human and baboon: V1/Vp =1.3, V2/Vp= 0.4. For dog and lamb: V1/Vp =1.0, V2/Vp= 0.3. “Kupffer” indicate liver Kupffer cells and “Sinusoidal” are liver parenchymal cells.(**A PK model with an additional liver compartment is used for recAP. *Clp for recAP corresponds to the liver metabolic clearance.)
Protein | Species | MW | Catabolic organ | Clp ml/m |
f1 | f2 | L1 ml/m |
L2 ml/m |
---|---|---|---|---|---|---|---|---|
Albumin | Human | 66,500 | Endothelium | 0.167 | 0.734 | 0.722 | 0.87 | 2.00 |
Monoclonal Antibody | Human | |||||||
Mepolizumab | 149,000 | Endothelium | 0.132 | 0.367 | 0.361 | 0.87 | 2.00 | |
Infliximab | 149,000 | Endothelium | 0.23 | 0.367 | 0.361 | 0.87 | 2.00 | |
Alkaline phosphatase | Human | |||||||
recAP** | 140,000 | Liver | 66.2* | 0.367 | 0.361 | 0.87 | 2.00 | |
Placental | 140,000 | Liver | 0.371 | 0.367 | 0.361 | 0.87 | 2.00 | |
Amylase | Baboon | 57,086 | Kidney | 27.9 | 0.734 | 0.722 | 0.87 | 2.00 |
Lipase | Baboon | 48000 | Kidney | 27.9 | 0.734 | 0.722 | 0.87 | 2.00 |
Alanine Transaminase | Dog | 54,600 | Sinusoidal | 0.949 | 0.530 | 0.535 | 1.2 | 2.71 |
Aspartate Aminotransferase | Dog | |||||||
Mitochondrial | 47,517 | Kupffer | 56.9 | 0.530 | 0.535 | 1.2 | 2.71 | |
Cytoplasmic | 46,247 | Sinusoidal | 4.06 | 0.530 | 0.535 | 1.2 | 2,71 | |
Creatine kinase | Dog | 81,000 | Kupffer | 31.7 | 0.370 | 0.374 | 1.2 | 2.71 |
Lactate Dehydrogenase | Lamb | |||||||
LD1 Heart | 138,000 | Sinusoidal | 0.975 | 0.53 | 0.53 | 3.85 | 1.35 | |
LD5 Skeletal muscle | 138,000 | Kupffer | 6.35 | 0.53 | 0.53 | 3.85 | 1.35 |