Office of Research Acceptable Volumes for Drug Administration - Office of Research

Acceptable Volumes for Drug Administration

Acceptable Volumes for Drug Administration

Purpose

The purpose of this policy is to provide researchers with the maximum daily acceptable volumes of fluids or compounds that may be administered to animals. These guidelines apply to healthy, adult animals. When immature of debilitated animals are used, the veterinary staff must be consulted.

Background

The administration of excessive dose volumes may produce pain, excitement, and altered physiological parameters (e.g., serum electrolyte imbalance, increased blood pressure, and increased respiratory rate), and cause abnormal compound absorption.

Policy

The following table provides acceptable (maximum)a daily cumulative volumes in ml/kg body weight*:

Species Oral Subcutaneous Intraperitoneal Intramuscular Intraveneous Bolus
(slow injection)
Mouse 10 (50) 10 (40) 20 (80) 0.05b (0.1)b 2(25)
Rat 10 (40) 5 (10) 10 (20) 0.1b (0.2)b 5 (20)
Rabbit 10 (15) 1 (2) 5 (20) 0.25 (0.5) 2 (10)
Dog 5 (15) 1 (2) 1 (20) 0.25 (0.5) 2.5 (5)
Macaque 5 (15) 2 (5) c (10) 0.25 (0.5) 2 (c)
Marmoset 10 (15) 2 (5) c (20) 0.25 (0.5) 2.5 (10)
Minipig 10 (15) 1 (2) 1 (20) 0.25 (0.5) 2.5 (5)
Fish 2 g/kgd 1 (c) c (10) c (0.05) 5 (c)

*Multiply the appropriate number above times the animal’s body weight in kg to obtain the maximum volume of administration.

NOTE: Values are in ml/kg unless otherwise specified.

a  For nonaqueous injectates, consideration must be given to the time of absorption before redosing. No more than two intramuscular sites should be used per day. Subcutaneous sites should be limited to two or three sites per day. The subcutaneous site does not include Freund’s adjuvant administration.

b Volumes in milliliters per site.

cData not available.

dAdministered via gel capsules.

Procedures

  •          In addition to the volume of administration, one must also consider the character of the solution. Known irritants such as Freund’s adjuvant must be delivered according to specific IACUC approved guidelines and protocols.
  •         Solutions above pH 8.0 and below pH 4.5 should be diluted or buffered even if this means exceeding guidelines, provided that veterinary and IACUC approvals have been obtained.
  •          A large intramuscular injection into a small muscle mass may force the dose into facial planes and subcutaneous tissues that may accelerate lymphatic drainage and may also cause pressure necrosis or nerve damage. It is preferred that more very small injections be given with small diameter needles (e.g. 25-27 gauge) versus one or two large injections.
  •          For parenteral routes of administration (a route other than oral), it may be less irritating to administer the dose halved in two separate locations. For studies requiring repeated parenteral dosing, the same site should not be used for two consecutive administrations.
  •          The maximum intradermal dose for all species is 0.05-0.10 mL/site.
  •          One must consider any possible effects attributable to the vehicle alone (e.g., dimethyl sulfoxide (DMSO) and polyethylene glycol).

References

  1. The Care and Feeding of an IACUC: The Organization and Management of an Institutional Animal Care and Use Committee – Whitney K. Petrie and Sonja L Wallace, CRC Press, 2015