Suositukset aineiden annosteluun ja verinäytteiden ottoon

 

 Suositeltavat neulan koko   

       sc - nahan alle
       im - lihakseen
       iv - suonensisäisesti
       ip - vatsaonteloon

 

Hiiri
   sc: 25 G        im: 27 G        iv: 26-28 G    ip: 25-27 G                

Rotta
   sc: 25 G        im: 25 G        iv: 25-27 G    ip: 23-25 G   

Kani
   sc: 21-25 G     im: 25 G     iv: 23-25 G     ip: 21-23 G      

Diehl et al: A GOOD PRACTICE GUIDE TO THE ADMINISTRATION OF SUBSTANCES AND REMOVAL OF BLOOD, INCLUDING ROUTES AND VOLUMES – Journal of Applied Toxicology 21, 15 - 23, 2001

Table 1. Administration volumes considered good practice (and possible maximal dose volumes) a.)

Species Route and volumes (ml/kg)
  Oral
 
s.c.
 
i.p.
 
i.m.
 
i.v.
(bolus)

i.v.
(slow inj.)

Mouse 10 (50) 10 (40) 20 (80) 0.05(0.1)b) 5 (25)
Rat 10 (40) 5 (10) 10 (20) 0.1 (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)(10)  0.25 (0.5)  2.5  (10)
 Minipig  10 (15)  1 (2)  1 (20)  0.25 (0.5)  2.5  (5)

 a.) For non-aqueous injectates, consideration must be given to 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.) Values in millilitres per site.
c.) Data not available.

Table 2. Repeated intravenous infusion: dose volumes/rates (and possible maximal volumes/rates) a.) 

Daily infucion period  Mouse  Rat      Rabbitb)  Dog  Macaque  Minipig
Total daily volume (ml/kg)           
 4 hL c)   L c)  20   L c)

20

  L c)   L c)
 24 h  96(192)  60(96)  24
(72)
 24(96)  60  24
Rate (ml kg-1 h-1)                 
 4 h  L c)  5  L c)  5 c)  L c)
 24 h  4 (8)  2.5(4)  1 (3)  1 (4)  2.5  1

a.) For non-aqueous injectates, see text. In some cases two sets of values are shown. Those in parentheses are the possible maximal values.
b.) Based on teratology studies.
c.) Data not available.

Table 3. Circulating blood volume in laboratory animals     

Species Blood volume (ml/kg)
  Recommended mean a) Range of means
Mouse 72 63-80
Rat 64 58-70
Rabbit 56 44-70
Dog (Beagle) 85 79-90
Macaque (Rhesus) 56 44-67
Macaque (Cynomolgus) 65 55-75
Marmoset 70 58-82
Minipig 65 61-68

 a.) The recommended mean corresponds to the mid-point of the range of means.

Table 4. Limit volumes and recovery periods  

Single sampling
(e.g. toxicity study)

Multiple sampling
(e.g. toxicokinetic study)

% Circulatory blood volume removed  Approximate recovery
 period
 % Circulatory blood volume removed in 24 h Approximate recovery period
7.5 % 1 week 7.5 % 1 week
10 % 2 weeks 10-15 % 2 weeks
15 % 4 weeks 20 % 3 weeks

    
Table 5. Total blood volumes and recommended maximum blood sample volumes for   species of given body weights  

Species
(weight)
Blood volume
(ml)
7.5%
(ml)
10%
(ml)
15%
(ml)
20%
(ml)
Mouse
(25 g)
1.8 0.1 0.2 0.3 0.4
Rat
(250 g)
16 1.2 1.6 2.4 3.2
Rabbit
(4 kg)
224 17 22 34 45
Dog
(10 kg)
850 64 85 127 170

Macaque (15 kg)
(Rhesus)

 280  21  28  42  56
Macaque (5 kg)
(Cynomolgus)
 325  24  32  49  65
Marmoset
(350 g)
 25  2.0  2.5  3.5  5
Minipig
(15 kg)
 975  73  98 146  195 

   

Table 6. Summary of the advantages and disadvantages of the various methods of blood sampling 

Route/vein General anaesth. Tissue damage a Repeated bleeds Volume Species
Jugular No Low Yes +++ Rat, dog, rabbit
Cephalic No Low Yes +++ Macaque, dog
Saphenous/lateral tarsal No Low Yes ++(+) Mouse/rat, mamoset/macaque, dog
Marginal ear  No (local)  Low Yes   +++ Rabbit, minipig
Femoral  No  Low Yes  +++  Marmoset/macaque 
Sublingual  Yes  Low Yes  +++  Rat 
Lateral tail  No  Low Yes  ++(+)  Rat, mouse, marmoset
Central ear artery  No (local)  Low Yes  +++  Rabbit 
Cranial vena cava  No  Low Yes  +++  Minipig 
Tail tip amputation
(<1-3mm)
 Yes  Mod Limited  Mouse/rat 
Retrobulbar plexus  Yes  Mod/high Yes  +++  Mouse/rat 
Cardiac b  Yes  Mod No  +++  Mouse/rat/rabbit 

a.) The potential for tissue damage is based on the likely incidence occurring and the severity of any sequelae, e.g. inflammatory reaction or histological damage.
b.) Only carried out as a terminal procedure under general anaesthesia.

Table 7. Recommended sites for repeated blood sampling  

Species Recommeded site
Mouse Saphenous, lateral tail
Rat Saphenous, lateral tail, sublingual
Rabbit Marginal ear, central ear artery, jugular
Dog Cephalic, jugular, saphenous
Macaque Cephalic, saphenous, femoral
Marmoset Femoral, saphenous
Minipig Cranial vena cava

   3.9.2014SM