The differences in metabolic rates (M) of different mammals often make it difficult to estimate the dose of e.g. anaesthetics from one species to another. It is well known that the mammalian metabolic rate is correlated to the body weight (W), and the relationship between body weight and metabolic rate kan be expressed using the equation:(1) M = 3.8 x W-25Using the assumption, that the dose of e.g. an anaesthetic only depends on the metabolic rate of the animal, a simple mathematic equation can be used in scaling the dose from one species to another:
As an example the equation is employed for the calculation of the doses of pentobarbital for a series of different mammals of different size. The calculated doses agree well with the doses reported in the literature. The equation may be of generel usefulness for a quick calculation of a suitable dose level, when the dose level of another species is known

Hau, J.

Poulsen, O. M.

English

Journals from University of Tartu

Scand. J. Lab Anim. Sci. No. 2 , 1988 . V01. 15Doses for Laboratory Animals based on Metabolic Rateby J. Ham and 0. M. Paulsen.Department of Veterinary Pathology, Laboratory Animal Unit, Royal Veterinary and AgriculturalUniversity, Copenhagen, B'ulowsvej 13, 1870 Frederiksberg C, Denmark.The development and use of laboratory animalmodels — applied laboratory science — is basedon the premise that animals of different speciesincluding man are more or less similar and thuscan be compared.It is well known that mammals in general havesimilar organ weights in proportion to their bo-dy size, and equally well known that the rate offunction of the various tissues and organs va-ries from one species to another.This variation renders it often difficult to esti—mate e.g. doses of anaesthetics or feed additi—ves from one species to another.In the many instances where metabolic func-tions are involved the problem of scaling maybe simplified significantly, and simple guideli-nes for calculating e.g. drug dosage from bodyweight are easy to outline.The metabolic rate refers to the energy metabo-lism per unit time. It can be calculated in diffe-rent ways, the most frequently used being thedetermination of oxygen consumption per timeunit.It has been known since 1930, that the metabo-_. 0lie rate of all mammals is correlated to the bodyweight raised to the 0.75 power.This correlation gives a straight line when therate of oxygen consumption is plotted againstbody weight in a double logarithmic plot with aslope of 0.75.Figure 1 (Schmidt-Nielsen 1975) shows the re-lationship between the rate of oxygen con—sumption per unit body mass of various mam-mals when plotted against body mass on loga—rithmic coordinates. Alternatively, the follo-wing equation may be used:(1) M : 3.8><W*0-25where M is the metabolic rate (oxygen con-sumption in ml 02 per gram body mass perhour) and W is the body weight in grams.1n the following example we have tried to makeuse of the relationship between metabolic rateand body weight for the estimation of doses ofpentobarbital in mammals of different size.This has been done with the assumption thatthe dose depends on body size and metabolicrate in the following manner: .0 I     SLOPE = —O.25 i I l0‘01 1 1001 0.1Oxygenconsumption(ml02g_‘h“)10 100 1000Body mass (kg)Figure 1. The rates of oxygen consumption of various mammals, when calculatedper unitbody mass and plotted against body mass on logarithmic coordinates, tend to fall along astraight regression line with a slope of —0,25, (Schmidt-Nielsen 1975).81Scand. J. Lab. Anim Sci. No. 2 . 1988 . Volt 15X w —0,25(2) —‘ = —’x2 W2-0-25orWl—OJS(3) X, = x2 x wz—wAs prototype we have chosen a monkey, bodyweight 10 kg and a pentobarbital dose of 25mg/kg.These data gives the equation(4) x1 = 25/10.0_25 x WywTable 1 compares the doses of pentobarbitalcalculated by equation 4 with doses for variousspecies reported in the literature. The doses cal—culated using the equation agree fairly wellwith the doses reported in the literature, exeptfor the dose for mice, which is much too high,when calculated by the formula. This is becau-se the 0.50 power of body weight should be em-ployed when dealing with animals having bodyweights below 100 g (Bartels 1982). Table 1Species/weight Dose calculated by Dosein g equation 4 in mg/kg from literaturein mg/kgMouse (25) 112 60-90Rat (350) 58 50-72Guinea pig (900) 46 30—40Rabbit (3000) 34 30—50Cat (3500) 33 25—30Monkey (10000) 25 by def. 25 def.Dog (11000) 24 25—30Goat (30000) 19 15—30Fig (50000) 17 10-25 Doses of pentobarbital calculated by equation 4,compared with doses suggested by Green (1979),Svendsen and Han (1981) and Ingebrigtsen andErichsen (1985).The formulas presented should be consideredas guidelines only. Some species react with par—ticular sensitivity towards .one or more drugsand variations in the reaction or animals withina species occur due to differences in sex, age,strain. stock, nutritional state, time of day,82stress level, type of bedding, ambient tempera—ture etc.It is however, our hope that this simple formuvla may be of assistance to laboratory animal ve—terinarians and scientists when they off the cuffhave to estimate doses for mammals of varioussizes and species.SammendragForskellen i forskellige pattedyrs metabolske rater(M) gar det ofte vanskeligt at estimere dosis af anae—stetika fra en art til en anden. Det er almindeligtkendt, at pattedyrs metabolske rate er relateret tilkropsvaegten (W), og relationen mellem kropsvaegt0g metabolsk rate kan udtrykkes ved formlen:(1) M = 3.8xW'0v25Under antagelse af, at dosis af f. eks. et anaestetikumalene afhaenger af dyrets metabolske rate, kan et sim-pelt matematisk udtryk anvendes ved beregning afdosis fra en art til andre arter:XI _ WI .025X; W2 70.25(2)orW] -o.25(3) x, 2 X; x W035Som eksempel anvendes formlen til beregning af dendosis af pentobarbital, der skal anvendes til en r&kkeforskellige dyrearteri De beregnede dosisva‘erdier er igod overensstemrnelse med de i litteraturen anbefale—de doser for de pagaeldende arter. Formlen er mulig—vis generel anvendelig til hurtigt at estimere et anven-deligt dosisniveau, hvis dosis kendes for en eller flerepattcdyrarter.SummaryThe differences in metabolic rates (M) of differentmammals often make it difficult to estimate the doseof e.g. anaesthetics from one species to another. It iswell known that the mammalian metabolic rate iscorrelated to the body weight (W), and the relations-hip between body weight and metabolic rate kan beexpressed using the equation:(1) M : 3.8><W’°-25Using the assumption, that the dose of e.g. an anaes—thetic only depends on the metabolic rate of the ani-mal, a simple mathematic equation can be used inscaling the dose from one species to another:  X W 4).:5(2) l = lX: W39”orW]»0‘15(3) X1 : X3 X @025As an example the equation is employed for the cal—culation of the doses of pentobarbital for a series ofdifferent mammals of different size. The calculateddoses agree well with the doses reported in the litera—ture. The equation may be of generel usefulness for aquick calculation of a suitable dose level, when thedose level of another species is known.Yhteen veto / Pe/konenErot eri elainlajien aineenvaihduntanopeuksissa (M)vaikeuttavat usein esim. Nukutusainema‘arien ar—viointia lajista toiseen. Tiedetaan hyvin, etta nisak—kaiden aineenvaihduntanopeus riippuu ruumiinpai—nosta (W) seuraavan kaavan mukaisesti:M : 3.8XW'025Oletettaessa, etta nukutusaineen annos riippuu vainelaimen aineen vaihduntanopeudesta, voidaan an-nos laskea lajista toiseen yksinkertaisen yhtalénavullaScand, 1 Lab. Anim. Sci. No. 2 . 1988 . Vol. 15Wl-ozsX, : x2 x w_,»0-25Esimerkin vuoksi yhtaléa 0n kaytetty pehtobarbi-taaliannosten laskemiseen erikokoisille nisakkaille.Lasketut arvot sopivat kirjallisuudessa annettujenkanssa hyvin yhteen. Yhtalésta voi 011a yleisesti hyd-tyél haluttaessa tehda nopea laskelma sopivasta an—nostasosta, kun toiselle eléiinlajille tarvittava annostunnetaan.ReferencesBarrels, H..' Metabolic rate of mammals equals the0.75 power of their body weight. Exp]. Biol.Med. 7, 1982,1—11.Green, C. J.: Animal Anaesthesia. Laboratory Ani~mal Handbooks 8, London, 1979.lngebrigtsen, K. & Erichsen, S..' Sedasjon, Anestesi0g Analgesi ved Dyreforsek. NFS publikasjonnr. 2, 1985.Schmidt—Nielsen, K.: Animal Physiology, Adapta-tion and Environment. Cambridge UniversityPress, 1975.Svendsen, P. & Hau, J.: Forsagsdyr 0g Dyreforszg.Odense Universitetsforlag, 1982. ' Falgende programmer er né tilgjengelige:Handling and basic techniques series:not include postage.Veterinaer Annelise HemMontebello, 0310 Oslo 3, NORGE VI FQLGER OPP SUKSESSENFELASA AUDIOVISUAL TRAINING PROGRAMMES — REPRINTED —AGAIN AVAILABLE in limited numbers — order now!FELASA audiovisuelle programmer er nyopptrykket og finnes na p5 lager.I hereby order the following tape/slide programme(s).................................................... NKR 3501. The laboratory mouse ................................................................................ NKR 3502. The laboratory rat ..................................3. The laboratory quinea pig .....................4. The laboratory rabbit ..............................5. The athymic nude mouse — breeding and maintenance ................................ NKR 325A handling charge of NKR 75,- is applied to all orders irrespective of size. The price does .................................................... NKR 350Dertil kommer et ekspedisjonsgebyr pé kr. 75,- pr. ordre samt porto.ETTERSPQRGSELEN ER STOR — BESTILL NA HOS:Dyreavdelingen, Det Norske Radiumhospital.............................................. NKR 350Mail to:  83

Doses for Laboratory Animals based on Metabolic Rate

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Doses for Laboratory Animals based on Metabolic Rate

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