2. Animal Dosing Guidelines

Animal Dosing Guidelines

  • Equivalent Dosage Caluculation
  • Common Dosing Volumes and Rates for Animal Experiments
  • Characteristics of Different Administration Routes
  • Common Usage Range of Solvents
Table 1

Equivalent Dosage Caluculation Guidelines[1][2]

Species
Body weight (kg) Working weight range (kg) Body surface area (BSA; m2) Km factor (a)
Mouse 0.020 0.011-0.034 0.007 3
Hamster 0.080 0.047-0.157 0.016 5
Rat 0.150 0.080-0.270 0.025 6
Guinea pig 0.400 0.208-0.700 0.05 8
Dog 10 5-17 0.50 20
Rabbit 1.8 0.9-3.0 0.15 12
Monkey 3 1.4-4.9 0.25 12
Baboon 12 7-23 0.60 20
Micro-Pig 20 10-33 0.74 27
Human 60 -- 1.62 37
Table Description:

a: Correction factor (Km), unit (kg/m2); Km (kg/m2) = Working weight range (kg) / Body surface area (m2).

Dose in Animal A (mg/kg) = Dose in Animal B (mg/kg) × (Km of Animal B /Km of Animal A)

Example: if the dose of compound X in mice is 20 mg/kg, the equivalent dose in rats can be calculated as follows:

Rat dose (mg/kg) = Mouse dose (20 mg/kg) × Km factor of mouse (3) / Km factor of rat (6) = 10.0 mg/kg

Note[2][3]

The above conversion method is provided for reference only: animals differ in absorption, distribution, metabolism, and excretion.

The Km value is an estimated correction factor and may not be identical to the actual measured or calculated values in animals.

Table 2

Common Dosing Volumes and Rates for Animal Experiments[4][5]

Species
 Administration Route Oral Gavage, mL/kg IV bolus, mL/kg IP, mL/kg SC, mL/kg IM, mL/kg ID, mL/site
Range Volume Volume Volume Volume Volume Volume
Mouse

 Ideal 10 5 5-10 1-5 0.1 0.1
Maximum 40 25 50 20 g 1 1
Rat

 Ideal 10 1 5-10 1 0.1 0.1
Maximum 20 20 20 20 10 0.1
Guinea pig

 Ideal 10 1 1-5 1-5 0.1 0.1
Maximum 30 5 20 10 0.5-1 0.1
Rabbit

 Ideal 1 1 3 1-2.5 0.1-0.5 0.1
Maximum 20 10 5 10 1 0.1
Dog

 Ideal 5 1 3 0.5 0.1-0.25 0.1
Maximum 20 10 5 2 1 0.1
Micro-Pig

 Ideal NIA 1 1 1 0.25 0.1
Maximum NIA 10 5 3 0.5 0.1
Macaque

 Ideal 5 1 3 0.5 0.1-0.5 0.1
Maximum 10 10 5 2 1 0.1
Table Description:

For IV administration or near volume limits, consider solution properties (e.g. pH). The recommended working range is pH 4.5–8.0.

pH tolerance varies by administration route in the following order: p.o. > i.v. > i.m. > s.c. > i.p.; animal health (e.g. kidney and cardiovascular function) should also be assessed. For IV infusion or when approaching volume limits, these systems must be normal to allow increased volume.

Intramuscular injection: no more than two sites per day.

Subcutaneous injection: two or three sites per day.

Yellow: Administration of larger volumes can be spaced out over time (e.g. 20 mL/kg four times daily, reaching a total of 80 mL/kg within 24 hours).

Blue: If the administered volume exceeds the commonly used range, it is recommended to split the dose across multiple sites.

Red:

Divide across multiple sites and alternate legs, with no more than five sites per leg. The final volume per site should not exceed 0.10 mL. Administration can also be split over time (e.g. 10 mL/kg four times daily, reaching a total of 40 mL/kg within 24 hours).

Purple: Not commonly used.

NIA: No information available.

Species
 Administration Route IV infusion, mL/kg Intravitreal, μL/eye Intra-articular, mL/joint Intranasal, μL/nostril
Range Volume Rate, mL/min Volume Joint Volume Volume
Mouse

 Ideal 50 1 2 NIA NIA 25
Maximum
Rat

 Ideal 50 1 5 Hock Joint 0.1 50
Maximum Tarsus 0.05
Guinea pig

 Ideal 10 1 NIA NIA NIA 100
Maximum
Rabbit

 Ideal 20 1 100 NIA 0.5 200
Maximum
Dog

 Ideal 20 5 100 Hock Joint 1 500
Maximum
Micro-Pig

 Ideal 10 1 NIA NIA NIA NIA
Maximum
Macaque

 Ideal 20 1 50 NIA NIA 200
Maximum
Table Description

For IV administration or near volume limits, consider solution properties (e.g. pH). The recommended working range is pH 4.5–8.0.

pH tolerance varies by administration route in the following order: p.o. > i.v. > i.m. > s.c. > i.p.; animal health (e.g. kidney and cardiovascular function) should also be assessed. For IV infusion or when approaching volume limits, these systems must be normal to allow increased volume.

Intramuscular injection: no more than two sites per day.

Subcutaneous injection: two or three sites per day.

NIA: No information available.

Table 3

Characteristics of Different Administration Routes (Mouse as Example)[4][5]

Dosing route Formulations Characteristics
Oral gavage

Clear solutions, co-solvents, suspensions, mini-tablets, capsules, or oily liquids.

Ensure uniform and stable formulation (pH range: 2–9).

Route: feeding needle or tube.

GI absorption; subject to GI and hepatic first-pass metabolism which can reduce bioavailability.
Intravenous (i.v.) Injection

Clear solutions;

nanosuspensions (defined particle size; free of embolism-inducing particulates)

Route: tail vein.

Directly into the vein, bypassing absorption; bioavailability is considered 100% with the fastest onset.
Subcutaneous (s.c.) Injection

Clear solutions preferred;

low-viscosity suspensions acceptable (pH 4–8; physiological pH ≈ 7.4 preferred).

Route: loose neck/back skin.

Absorbed near capillaries; reaches circulation by diffusion/filtration; slower absorption but longer-lasting; avoids GI and hepatic first-pass metabolism.
Intraperitoneal (i.p.) Injection

Clear solutions preferred;

homogeneous suspensions acceptable; physiological pH recommended.

Route: peritoneal cavity (sensitive site).

No GI first-pass metabolism, but hepatic first-pass metabolism still occurs; relatively high bioavailability.
Intramuscular (i.m.) Injection

Clear solutions preferred;

low-viscosity suspensions acceptable (pH 2–9; physiological pH ≈ 7.4 preferred).

Route: limb muscle.

Improper technique or accidental nerve injection may cause paresis, paralysis, or muscle necrosis.
Intraarticular (i.a.) Injection

Clear solutions preferred;

suspensions (e.g. emulsions and liposomes) acceptable.

 Route: targeted injection into the hock joint.
Intratracheal (i.t.) Injection

Clear solutions preferred;

suspensions must be aerosolized/nanosized to reduce particle size.

Route: delivery from the trachea into the bronchi and lungs.

Sedation/anesthesia often required to minimize struggling.
Table 4

Common Usage Range of Solvents[2][6]

Product Name Dosing route/common usage range
DMSO 10-20% (oral, i.v.)
NMP–N-methylpyrrolidon 10-20% (oral, i.v.)
PEG300 40-100% (oral, i.v.)
Tween 80 5-10% (oral, i.v.)
SBE-β-CD 20-40% (oral, i.v.)
HP-β-CD 20-40% (oral, i.v.)
D5W 5% Dextrose in water oral, i.v.
Cremophor EL 5-10% (oral, i.v.)
Product Name Dosing route/common usage range
Cremophor RH40-Polyoxyl 40
hydrogenated castor oil
5-10% (oral, i.v.)
Solutol HS-15
(Polyethylene glycol
12-hydroxystearate)		 20-50% (oral, i.v.)
Gelucire 44/14 20-50% (oral)
Lecithin-phosphatidylcholin 20-50% (oral, i.v.)
Mid-chain triglyceride of
caprylic/caprolic acid		 60-100% (oral); 20-40% (i.v.)

References:

[1] Ken Wojcikowski, et al. Animal studies on medicinal herbs: predictability, dose conversion and potential value. Phytother Res. 2014 Jan;28(1):22-7.  [Content Brief]

[2] Ping Li, et al. Developing early formulations: practice and perspective. Int J Pharm. 2007 Aug 16;341(1-2):1-19.  [Content Brief]

[3] Anroop B Nair, A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm. 2016 Mar;7(2):27-31.  [Content Brief]

[4] Shayne Cox Gad, et al. Tolerable Levels of Nonclinical Vehicles and Formulations Used in Studies by Multiple Routes in Multiple Species With Notes on Methods to Improve Utility. Int J Toxicol. 2016 Mar-Apr;35(2):95-178.  [Content Brief]

[5] K H Diehl, et al. A good practice guide to the administration of substances and removal of blood, including routes and volumes. J Appl Toxicol. 2001
Jan-Feb;21(1):15-23.  [Content Brief]

[6] Patricia V Turner, et al. Administration of substances to laboratory animals: routes of administration and factors to consider. J Am Assoc Lab Anim Sci. 2011 Sep;50(5):600-13.  [Content Brief]