| | Suositukset aineiden annosteluun ja verinäytteiden ottoonInjektiovolyymit ja neulan koko sc - nahan alle im - lihakseen iv - suonensisäisesti ip - vatsaonteloon Hiiri sc 25 G 0,5 ml im 27 G 0,05 ml iv 26-28 G 0,3 ml ip 25-27 G 2-3 ml po 0,5 ml Rotta sc 25 G 2 ml im 25 G 0,1 ml iv 25-27 G 0,5-1 ml ip 23-25 G 4-10 ml po 2 ml Kani sc 21-25 G 1-5 ml/kohta, yht. 20-30 ml im 25 G 0,5 ml iv 23-25 G 10 ml ip 21-23 G 50 ml 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 infusion period | Mouse | Rat | Rabbit b.) | 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 | L 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-1) | | 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 (Rhesus) (15 kg) | 280 | 21 | 28 | 42 | 56 | Macaque (Cynomolgus) (5 kg) | 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 anaesthesia | Tissue damage a.) | Repeat bleeds | Volume | Species | Jugular | No | Low | Yes | +++ | Rat, dog, rabbit | Cephalic | No | Low | Yes | +++ | Macaque, dog | Saphenous/ lateral tarsal | No | Low | Yes | ++(+) | Mouse/rat, marmoset/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 (<1-3 mm) | 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 | Recommended 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 |
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