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Absorption inputs Currently, the model accommodates four routes of administration - oral, intramuscular (IM), intravenous (IV) and subcutaneous (SC) only. The options for absorption inputs follow based on the selected route of administration.

⋇ Oral administration

Oral inputsOn selecting oral route of administration, two options for absorption appear. The first one is absorption type and the second to enter the respective value.
The most common in vitro experiments to assess the drug's apparent permeability (P app) through the small intestine across the apical-basolateral layer is using cell monolayers such as Caco-2 or MDCK cells. The values are generally reported as cm.s-1. If this data is not readily available, polar surface area (PSA) and hydrogen bond donors (HBD) can be used.
PSA inputsPolar surface area (PSA) is the sum of the surface area of all the polar atoms consisting mainly oxygen and nitrogen including any attached hydrogen atoms in a drug. The value entered should be in sq. angstroms (Ų).
Hydrogen atoms connected to the donor sites are considered as hydrogen bond donors (HBD). The input value in the model takes the number of hydrogen bond donors.
The effective permeability (Peff, in cm.s-1) of the drug is the in vivo permeability in humans. This Peff is computed using IVIVE obtained from various literature sources as follows:

For Caco-2,1log Peff= 0.6836 ×log Papp - 0.5579[ 1 ]

For MDCK,2log Peff= 0.829 × log Papp - 1.30[ 2 ]

PSA & HBD,5log Peff= -2.546 - 0.011 × PSA - 0.278 × HBD[ 3 ]

LogP, PSA & HBD,5log Peff= -3.067 + 0.162 × LogP - 0.010 × PSA - 0.235 × HBD[ 4 ]

The rate of absorption (Kₐ, in h-1) in humans is computed using Peff as follows:3

Kₐ = 2 × Peff / R[ 5 ]

The user is required to select the type of absorption input that is being provided. The corresponding absorption value should be entered for the selected absorption type (in the appropriate unitsi.e. either in ×10⁻⁶ cm.s-1or Ų or h-1). If there is no apparent permeability available for the drug, an option to enter the Kₐ value is also provided. This scalar would multiply the absorption rate (Kₐ) by the provided input.
There is also an option to adjust the absorption value using the optional box under the 'Optional tab' to input any scalar ('Absorption scalar').
Please note: This absorption value would remain constant for the entire simulation. Currently, the model does not have any transporter data or induction/inhibition included.
Note: If the apparent permeability value is 15 × 10⁻⁶ cm.s-1, please enter 15 for Caco-2 and 150 for MDCK cells. The model would then multiply this value by ×10⁻⁶ ×10⁻⁷ respectively.

⋇ Infusion

Infusion requires one more input - infusion time (in hours). If the time of infusion is zero, then this administration is treated as IV bolus.

⋇ Intravenous

Selection of an intravenous (IV) route does not require further absorption inputs as the model considers the provided dose as IV bolus.

⋇ Intramuscular

Upon selection of intramuscular (IM) administration, an input box to include IM release rate is provided. By default, the value is 0.0 and the units are in h-1.
The model currently assumes a first-order release rate from the IM depot (a standard depot volume of 4 mL is assumed for humans and 1 mL for rats and mice) which releases the drug into the surrounding muscle that subsequently distributes across the body as described in Rajoli et al.4

⋇ Subcutaneous

The model follows a similar pattern as the intramuscular administration with a first-order release from the subcutaneous compartment, but the drug releasing into the surrounding adipose compartment.


  1. Sun D, Lennernas H, Welage L, Barnett J, Landowski C, Foster D, et al. Comparison of Human Duodenum and Caco-2 Gene Expression Profiles for 12,000 Gene Sequences Tags and Correlation with Permeability of 26 Drugs. Pharmaceutical Research. 2002;19(10):1400-16.
  2. Gertz M, Harrison A, Houston JB, Galetin A. Prediction of Human Intestinal First-Pass Metabolism of 25 CYP3A Substrates from In Vitro Clearance and Permeability Data. Drug Metab Dispos 2010 July 1, 2010;38(7):1147-58.
  3. Yu LX, Amidon GL. A compartmental absorption and transit model for estimating oral drug absorption. Int J Pharm. 1999;186(2):119-25.
  4. Rajoli RK, Back DJ, Rannard S, Freel Meyers CL, Flexner C, Owen A, et al. Physiologically Based Pharmacokinetic Modelling to Inform Development of Intramuscular Long-Acting Nanoformulations for HIV. Clin Pharmacokinet. 2015 Jun;54(6):639-50.
  5. Winiwarter S, Bonham NM, Ax F, Hallberg A, Lennernäs H, Karlén A. Correlation of Human Jejunal Permeability (in Vivo) of Drugs with Experimentally and Theoretically Derived Parameters. A Multivariate Data Analysis Approach. Journal of Medicinal Chemistry. 1998;41(25):4939-49.