This article was downloaded by: [146.111.24.249]On: 09 April 2014, At: 05:54Publisher: Taylor & FrancisInforma Ltd Registered in England and Wales Registered Number: 1072954 Registered office: MortimerHouse, 37-41 Mortimer Street, London W1T 3JH, UK

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Pharmacokinetics and bioavailability ofdoxycycline hyclate after oral administration incalvesL A. Meijer a , K. G F. Ceyssens , B. I. J. A. C. de Grève & W. de Bruijna Dopharma Research B. V. , Zalmweg 24, Raamsdonkveer, 4941 VX, theNetherlands , +31 16 21 48 8Published online: 01 Nov 2011.

To cite this article: L A. Meijer , K. G F. Ceyssens , B. I. J. A. C. de Grève & W. de Bruijn (1993) Pharmacokineticsand bioavailability of doxycycline hyclate after oral administration in calves, Veterinary Quarterly, 15:1, 1-5, DOI:10.1080/01652176.1993.9694358

To link to this article: http://dx.doi.org/10.1080/01652176.1993.9694358

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ORIGINAL PAPERS

PHARMACOKINETICS AND BIOAVAILABILITYOF DOXYCYCLINE HYCLATE AFTER ORALADMINISTRATION IN CALVES

L. A. Meijer1, K. G. F Ceyssens, B. I. J. A. C. de Greve and W de Bruijn

Original Papers

SUMMARYThe bioavailability and pharmacokinetics of doxycyclinehyclate were determined in calves with immature rumenfunction. The bioavailability of doxycycline after oraladministration in a milk replacer was approximately 70%.The elimination half-life of doxycycline was found to be 9.5± 3.0 h. after intravenous administration, and 12.6 ± 5.0 h.after single oral administration. Plasma concentrations weredetermined after repeated oral administration of doxycy-dine dissolved in a milk replacer, at a dose of 5 mg per kgbody weight, twice daily. During the period of administra-tion, the plasma concentrations varied between Crnin of 1.0 ±0.19 mg/L and C,. of 2.3 ± 0.19 mg/L.

INTRODUCTIONDoxycycline is a broad-spectrum antimicrobial drug whichbelongs to the tetracyclines and acts against Gram-positive andGram-negative bacteria, protozoa and mycoplasma. Doxycy-cline has been used successfully for more than 20 years in humanmedicine (1, 2, 14). Doxycycline has better pharmacologicalproperties than other tetracyclines, such as oxytetracycline andis gaining a place in veterinary medicine. Positive results havealready been published for its use in pneumonia caused byPasteurella haemolytica (6), anaplasmosis (10) and heart water(9) in cattle; enzootic pneumonia in pigs (18), and ornithosis (3),colibacillosis (4) and chronic respiratory disease (8) in poultry.On the basis of MIC values, therapeutic plasma levels are 0.5 -1.0 mg/L (11, 12, 13, 18).Only a few reports have been published (6, 5, 19) about thepharmacokinetics of doxycycline, especially in preruminantcalves. Ziv and Sulman (19) and Riond et al. (15) havedescribed the pharmacokinetic properties of doxycycline afterintravenous administration. The oral use of doxycycline incalves has been briefly described by van Gool et aL (6). Theobjectives of this study were to determine the bioavailability ofdoxycycline hyclate after oral administration in a milk-replacerto preruminant calves, and to evaluate plasma concentrations ofdoxycyline when doxycycline hyclate is given to calves in amilkreplacer at a dose of 5 mg per kg body weight twice daily,for five consecutive days.

Corresondence should be send to: LA. Meyer, Dopharma Research B.V., Zabnweg 24,4941 VX Raamsdonkveer, the Netherlands. Phone +31 16 21 48 8Tentofeed 11, Tentego B.V, Mydrecht, the NetherlandsDopharma B.V., Raamsdonksveer, the Netherlands.

1 THE VETERINARY

Veterinary Quartely 1993; 15: 1-5

MATERIAL AND METHODSAnimalsFor all experiments four clinically healthy 3-month-old maleFriesian-Holstein veal calves with immature rumen functionwere used. The animals were housed in individual calfboxes andwere fed liquid milk replacer 2 twice daily. The calves wereweighed before each experiment, to ensure correct individualdosing of the animals. Their mean body weight at the beginningof the trials was 144 kg (153, 141, 143 and 140 kg). To facilitateblood collection at different times and to reduce irritation, anindwelling cannula was inserted in the left jugular vein of eachcalf under xylazine sedation (0.05 mg/kg body weight, intrav-enous) and local anaesthesia with lidocaine. The trials startedthe day after surgery, when the animals had recovered. Thewash-out period between the experiments was at least one week.

BioavailabilityTo determine the bioavailability of doxycycline administered asDoxycycline Hyclaat 20V (containing doxycycline hyclate anda water-soluble monosaccharide carrier), two experiments werecarried out :

Experiment I. Intravenous administrationFour calves received doxycyline hyclate as a 5% solution inphysiological saline through the venous cannula at a dose of 5mg per kg body weight. The duration of injection wasapproximately 30 to 40 seconds. After administration, thecannulas were flushed with 5 ml isotonic saline solution toprevent drug residues remaining in the cannula. Blood samples(22 in total) were obtained from each calf via the venouscannula before, at 10, 20, 30, 40, 60 minutes and 2, 3, 5, 7, 9, 12,14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours after theadministration of doxycycline. Immediately after collection ofeach sample the cannulas were flushed with isotonic salinesolution, and, if the time between two collections was longerthan 60 minutes, the cannulas were filled with 2 ml of heparin-solution. Blood samples were collected in 5-ml EDTA KMonovettes and were centrifuged immediately. Plasma wastransferred to glass screw-top vials and frozen at -20 °C untilanalysis.

Experiment 2. single oral administrationThe same four calves received a single oral administration ofdoxycyline hyclate dissolved in one third of their normal milkration at a dose of 10 mg per kg body weight. The other part oftheir ration was given after they had finished the medicatedportion. Blood samples (16 in total) were obtained from eachcalve via the venous cannula before, at 30, 60 minutes and 2, 4,6, 8, 10, 13, 15, 18, 21, 24, 27, 30, 33 and 36 hours after dosing.The blood samples were handled and stored as in experiment 1.

QUARTERLY. V01.15. No.1, MARcii. 1993

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Plasma concentrations after repeated oral dosingTo evaluate the range of plasma concentrations achieved afterrepeated dosing, the same four calves received uoxycyclinehyclate dissolved in one third of their normal milk ration at adose of 5 mg doxycycline HCI per kg body weight twice daily,ateach feeding time, for five consecutive days. The mean durationof the administration was approximately 4 minutes. During theexperiment, 30 blood samples were obtained from each calf viathe venous cannula. Sample collection and storage was asdescribed for experiment -I-. During the five days of administra-tion, blood samples were collected just before the medicatedmilk was given.

AnalysisThe concentration of doxycycline in the plasma samples wasdetermined by high-performance liquid chromatography with aPLRP-S column, 150*4.6 mm ID, particle size 5p, (PolymerLaboratories) at ambient temperature. The mobile phase wasprepared by mixing 400 ml of water, adjusted to pH=1.8, 170ml of acetonitrile and 430 ml of methanol. After dissolving 3 gheptane-sulphonic acid sodium salt per litre, the mobile phasewas filtered and degassed, using a vacuum manifold. The flowrate was kept at 1.0 ml/min. A diode-array detector (operated at344 nm) was used for the detection of doxycycline.Plasma samples were deproteinized by mixing 500 Al plasmawith 500 l cold 20% trichloroacetic acid in methanol. Aftermixing, the samples were placed in an ice bath for 10 minutes.The test samples were centrifuged for 10 minutes at 3000 g (4°C) and the supernatant was injected onto the column.Calibration curves were prepared by adding known amounts ofdoxycycline to 'blank' plasma obtained from calves of about thesame age as the experimental animals. The analysis procedurewas identical to that for test samples.The mean recovery of the described procedure, determined byassay of plasma samples with known amounts of doxycycline,was 100.4% (table 1).

Table 1. Recovery of doxycycline from spiked plasma samples. (n=7)

c, C, Mean S.D. V.C. MeanRecovery

0.47 0.47 0.47 0.0477 10.04 100.212.37 2.48 2.39 0.0694 2.90 100.984.74 5.01 4.72 0.2407 5.10 99.62

23.72 24.59 23.92 0.7928 3.31 100.86

C, Concentration of spiked samples (mg/L)C, Determined Concentration (mg/L)S.D. Standard DeviationV.C. Coefficient of Variation

The repeatability of the method, defined as the closeness ofagreement between replicate analyses of the same sample andexpressed as a coefficient of variation, was better than 2.5%(table 2).The detection limit was 0.095 mg doxycycline per litre plasma.The limit of quantification was 0.192 mg/L plasma.

CalculationsAfter analysis of the plasma samples, the concentration-timecurves were fitted according to an one, two or three compart-ment elimination model, using the non-linear regression moduleof SYSTAT 4.0. The optimum number of first-order rateprocesses in the predictive equation was selected on the basis ofthe residual sum of squares and the minimal Akaike's informa-

Table 2. Repeatability of measurements of doxycycline in spiked plasmasamples (concentrations in mg/L plasma, n = 51.

Sample 1 2 3 4

Mean 0.51 2.33 4.72 23.74SD 0.01 0.02 0.02 0.01VC 2.46 0.75 0.48 0.06S.D. Standard DeviationV.C. Coefficient of Variation

tion criterion. The equation for best-fitting models of theconcentration-time curves are listed below (equations 1 and 2).The bioavailability of doxycycline after a single oral administra-tion was calculated as the ratio of the area under the plasma-timecurve (AUC) after oral administration to the AUC afterintravenous administration, corrected for the dose (formula 3).The curve for the repeated oral administration was simulated,based on Ka and Ke as calculated for the first and lastadministration.

formulas:

I. mathematical model for three-compartment elimination withfirst order kinetics:

Y Me(-a*T)+ B*e(-13*T)+ C*(--y-r)A extrapolated plasma concentration at 1=0 for first

elimination phasea = elimination rate constant first elimination phaseB = extrapolated plasma concentration at T=0 for second

elimination phase= elimination rate constant second elimination phase

C = extrapolated plasma concentration at T=0 for thirdelimination phase

= elimination rate constant third elimination phaseT = time after administrationY = concentration doxycycline in plasma

2. mathematical model for resorption and two-compartmentelimination with first-order kinetics:

A

a

= A*e(-0,*T)-F B*6-I3*T)+ (A+B)*e(-79.)extrapolated plasma concentration at T=0 for firstelimination phase

= elimination rate constant first elimination phase= extrapolated plasma concentration at T=0 for second

elimination phaseelimination rate constant second elimination phaseresorption rate constanttime after administrationconcentration doxycycline in plasma

=Ka =T =Y =

3. bio-availability F:

F AUC oral * Dose IV * 100%,AUC iv Dosal oral

dose doxycline

weight calf (kg)

4. elimination half-life:

terminal T 1/2 0'693K,

K ,= elimination rate constant of last detected elimination phase

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R ES U LTS

The pharmacokinetic parameters were calculated for eachindividual animal.The concentration-time curves of doxycycline after intravenousadministration were fitted according a three compartmentmodel. The calculated pharmacokinetic parameters for eachanimal are listed in table 3.

Table 3. Pharmacokinetic constants for the disposition of doxycycline aftersingle intravenous administration to calves at a dose of 5 mg/kg bodyweight.

Calf 76 Calf 77 Calf 78 Calf 80 Mean ± S.D.

A (mg/L) 159.38 270.10 245.40 126.70 200.40 ± 59.16a (1/min) 0.2598 0.2685 0.276 1.117 0.4803 ± 0.3676B (mg/L) 2.29 2.83 1.01 2.39 2.13 ± 0.68

(1/min) 0.00659 0.02541 0.006638 0.00458 0.01080 ± 0.00847C (mg/L) 0.56 1.18 1.80 1.27 1.20 ± 0.447 (1/min) 0.000794terminal

(h) 14.5

0.001333

8.7

0.001739

6.6

0.001412

8.2

0.001319

9.5

± 0.000339

± 3.0Weight (kg) 153 141 143 140 144 ± 5

AUC

(meanie/L) 1662.5 2004.4 2076.4 1533.9 1819.3 ± 227.2

The mean plasma doxycycline concentration-time curve afterintravenous administration is plotted in figure 1.

4

3.5 -

1.5 -

0.5 -

IIIIIII 10.4 0.8 1,2 1.6

(Thousands)time after administration (min)

0 observed +/- SD fitted

2 2.4 2.8

Figure 1. Mean observed and fitted plasma concentration after intravenousadministration of 5 mg doxycycline per kg body weight.

The concentration-time curves of doxycycline after single oraladministration were fitted according a two-compartment modelwith first-order resorption: The calculated pharmacokineticparameters for each animal are listed in table 4.

The mean plasma doxycycline concentration-time curve aftersingle oral administration is plotted in figure 2. The meanbioavailability was 69 ± 12%.

A representative example of a plasmaconcentration-time curveafter repeated oral administration is shown in figure 3. Themeasured minimum and maximum plasmaconcentrations arepresented in table 5.

Table 4. Pharmacokinetic constants for the disposition of doxycycline aftersingle oral administration to calves at a dose of 10 mg/kg body weight.

Calf 76 Calf 77 Calf 78 Calf 80 Mean ± S.D.

A (mg/L) 200.00 80.00 81.25 11.09 93.09 ± 67.94a (1/min) 0.003929 0.004744 0.012424 0.004389 0.006371 ± 0.003506B (mg/L) 0.48 1.74 6.07 1.61 2.36 ± 2.18

(1/min) 0.006063 0.000843 0.002314 0.000901 0.001166 ± 0.000671K. (1/min) 0.004099 0.005146 0.012424 0.008357 0.007506 ± 0.003243Crnan (mg/L) 3.36 3.27 3.36 3.30 3.32 ± 0.04Trna, (min) 258 232 166 178 209 ± 38AUC(mg*min/L)

2780.1

terminal tI/2(h) 19.0

3028.6

13.7

2132.9

5.0

2344.5

12.8

2571.5

12.6

± 352.3

± 5.074 78 49 76 69 ± 12

3.5

3 -

2.5 -

1.5

0.5 -

0

0 IT0 0.4 0.8 1.2 1.6 2

(Thousands)administrationtime after (min)

0 observed +/- SD - fitted

2.4 2.8

Figure 2. Mean observed and fitted plasma concentration after a single oraldose of 10 mg doxycycline per kg body weight.

Table 5. Minimum and maximum plasmaconcentration of doxycycline afterrepeated oral administration to calves at a dose of 5 mg/kg body weight,twice daily.

Calf 76 Calf 77 Calf 78 Calf 80 Mean ± SD

(mg/L) 1.0 1.3 0.8 0.9 1.0 ± 0.19C.xx(mg/L) 2.2 2.6 2.1 2.4 2.3 ± 0.19

DISCUSSIONLittle is known about the pharmacokinetic behaviour ofdoxycycline in food-producing animals. Ziv and Sulmandetermined the elimination half-life of doxycycline to be 9.24 ±1.0 h after intravenous administration to cows and ewes (19).After intravenous administration to calves with mature andimmature rumen function, Riond et aL found an eliminationhalf-life of doxycycline of 14.9 ± 0.9 and 9.9 ± 0.6 h,respectively (15). In our experiment the calculated meanterminal t ih of doxycycline after intravenous administration topreruminant calves was 9.5 ± 3.0 h. The plasma time curve wasbest described by a three-compartment model. If these data were

T 1I.F. V E T E R I N A R Y Q U A R T E R L Y , V o i . 1 5 . N o . 1 , M A R C H , 1 9 9 3

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fitted according a two-compartment model, the calculatedpharmacokinetic parameters were comparable to those foundby Riond et al (15). The pharmacological relevance of the twodistribution phases we found is open to question, but there wasno statistical reason to neglect the detected a phase and use atwo-compartment model. The short a-phase was based on onlytwo or three measuring points and this could explain the ratherhigh standard deviation of this elimination rate constant.

3

2.8

2.6

2.4

2.2

2

1.8 -

1.6 -

1.4 -

1.2 -

0.8

0.6

0.4

0.2 -

0 90 2 4 6

(Thousands)time after first administration (min)

0 observed - fitted

8 10

Figure 3. Observed and simulated plasma concentration after repeated oraldoses of 5 mg doxycycline per kg body weight twice daily to calf 76.

The calculated mean terminal t ,/, of doxycycline after singleoral administration was 12.6 ± 5.0 h. for preruminant calves.The half-life times of the a and fl phase corresponded well to the/3 and 7 phase after intravenous administration, indicating agood absorption. The absorption of doxycycline was rather fast(Ka = 0.007506 ± 0.003243), with maximum blood levels of3.32 ± 0.04mg/L being reached after 209 ± 38 minutes. Theelimination and absorption rate constants calculated for calf 78were significantly different (P=0.05, Student's T-test) from themean of the other three animals and the standard deviationsgiven in table 4 were largely caused by animal 78. Groothuis (7)reported that the pharmacokinetics of drugs given orally tocalves in a milk replacer can be influenced by clotting of the milkin the abomasum and by the efficacy ofthe oesophageal groovereflex. These effects could explain the differences found betweenthe experimental animals. The somewhat low AUC of calf 78also resulted in a relative low bioavailability.After repeated oral administration of doxycycline to prerumi-nant calves in a dosage of 5 mg doxycycline per kg body weight,twice daily, plasma concentrations were detected with a C,,,,a of1.0 mg/L and a Cma, of 2.3 mg/L. This shows that the useddosage regimen results in therapeutic plasma levels for suscep-tible microorganisms (11,12,13,18).In the literature a bioavailability of 95% is described fordoxycycline after oral administration in humans (5). Van Goolet aL reported a value of 80 - 90% after oral administration tocalves (6). In our experiment, the mean bioavailability ofdoxycycline hyclate was calculated to be 69 ± 12% whenadministered in milk given to preruminant calves. Discrepanciesin the different values for bioavailability are commonly encoun-tered in the literature and are often related to the variouspharmacokinetic curve-fitting routines and analytical tech-niques used. Van Gool et al (6) used a different mathematical

approach for calculating the pharmacokinetic parameters, butthe mean calculated bioavailability of doxycycline hyclate iscomparable to that obtained in our study.Many studies have been performed on the kinetic behaviour andbioavailability of oxytetracycline. From a theoretical point ofview, it may be assumed that doxycycline will have a betterbioavailability than oxytetracycline after oral administration inmilk. Not only has doxycycline a better lipid solubility (5), butits absorption is also much less affected by the presence ofbivalent cations in food (15). Cations differ in their ability toreduce doxycycline absorption: calcium and zinc do not have amarked effect on absorption, whereas iron decreases absorptionmarkedly. Calcium and zinc may shorten the elimination half-life by irreversibly binding intestinally excreted doxycycline inthe intestinal lumen, thereby preventing enterohepatic cycling(17).Schifferli et al. determined the bioavailability of oxytetracyclineadministered orally to calves in a milkreplacer, to be 46 ± 12%(16). The calculated value for the bioavailability of doxycyclinein the presented study was about 70%, and was, as could beexpected, better than that of oxytetracycline.

The used doxycycline hyclate formulation had a good bioavaila-bility, even when administered in a milkreplacer. Plasmaconcentrations obtained during the repeated oral administrationindicate that doxycycline could be a valuable antimicrobial drugfor use in veterinary medicine.

REFERENCES1. Aronson AL. Pharmacotherapeutics ofthe newer tetracyclines..1 Am Vet

Med Assoc, 1980; 176: 1061-8.2. Cunha BA, Sibley CM, and Ristuccia AM. Doxycycline. Ther Drug Monit.,

1982; 4: 115-35.3. Dorrestein GM. Studies on pharmacokinetics ofsome antibacterial agents

in homing pigeons (Columbia livia). Thesis (1986): 83-102, 187-92.4. George BA, Fagerberg DJ, Quarles CL, and Fenton JM. Comparison of

therapeutic efficacy of doxycycline, chlortetracycline and lincomycin-spectinomycin on E.coli infection of young chickens. Poultry Sci, 1977; 56:452-8.

5. Goodman Gilman A, Goodman LS, Rail TW, and Murad F. Tetracyclines.The Pharmacological Basis of Therapeutics, 7th ed.; Macmillan PublishingCo., New York, (1985): 1170-9.

6. Gool F van, Santoul C, and Raynaud JP. Characteristiques pharmacocine-tiques et Bilan des essais cliniques pour le traitement du la metaphylacie desbronchopneumonies infectieuses des veaux de boucherie par le Ronaxan.Procedings of the 14th World Congress on Diseases of Cattle, Dublin, 1,1986: 627-31.

7. Groothuis DG. De pharmacokinetiek bij vleeskalveren en de activiteit vanantibacteriele middelen met betrekking tot Salmonella dublin infecties.Thesis Utrecht, 1983.

8. Harada Y. Performance studies on a medication program with oxytetracy-cline/doxycycline combination for prevention of Myoplasma gallisepticuminfection in breeding chickens. J Jap Vet Med Ass 1985; 38: 788-92.

9. Immelman A, Dreyer G. The use of doxycycline to control heartwater insheep. J South African Vet Assoc, 1982; 53 (I) 23-4.

10. Kuttler KL, and Simpson JE. Relative efficacy of two oxytetracyclineformulations and doxycycline in the treatment of acute anaplasmosis insplenectomized calves. Am J Vet Res, 1978; 39 (2).

11. Mandell GL, Douglas RG, and Bennet JE. Anti-infective Therapy, 1985:150-2.

12. Otten H, Plempel M, and Siegenthaler W. Antibiotica-Fibel, 1975: 347.13. Pijpers A, Klingeren B van, Schoevers EJ, Verheijden JHM, and Miert

ASJPAM van. In vitro activity of five tetracyclines and some otherantimicrobial agents against porcine respiratory tract pathogens. J VetPharmacol Therap, 1989; 12: 267-76.

14. Riond JL, and Riviere JE. Pharmacology and toxicology of doxycycline.Vet Hum Toxicol, 1988; 30 431-44.

15. Riond JL, Tyczkowska K, and RIVIERE E. Pharmacokinetics andmetabolic inertness of doxycycline in calves with mature or immaturerumen function. Am J Vet Res, 1980; 50 (8): 1329-32.

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16. Schiffer li D, Galeazzi RL, Nicolet J, and Wanner M. Pharmacokinetics ofoxytetracycline and therapeutic implications in veal calves. J Vet PharmacolTherap, 1982; 5: 247-57.

17. Shaw DH, and Rubin SI. Pharmacologic activity of doxycycline. J Am VetMed Assoc 1986; 189 (7): 808-10.

18. Takahashi K, Kuniyasu C, Yoshida Y, and Momotani E. Sensitivity in vitro

to macrolide antibiotics and tetracyclines of Mycoplasma hyopneumoniaeisolated from Pneumonia porcine lungs. Nat Inst Anim Hlth Quart 1978;18: 41-2.

19. Ziv G, and Sulman FG. Analysis of Pharmacokinetic Properties of NineTetracycline Analogues in Dairy Cows and Ewes. Am J Vet Res, 1974; 35(9): 1197-1201.

THE RELATIONSHIP BETWEEN DECREASE INFEED INTAKE AND INFECTION WITHTRYPANOSOMA CONGOLENSE AND T. VIVAX INWEST AFRICAN DWARF GOATS

G.J.Wassink,,I.S.Mornah2,0.Z wart', and T.Wensing3

SUMMARYTwenty-three mature dwarf goats were used to studywhether there is a relationship between the decrease in feedintake for individual goats and infection with T.congolenseand T.vivax. Furthermore, it was investigated how rectaltemperatures and blood parameters were affected by theT.congolense infection and how changes in theseparameterscan be used to predict the effect of a T vivax infection on feedintake.For individual goats a ranking correlation was foundbetween relative dry matter intake and infection (r=0.59;p<.05). Animals with the most marked decrease in drymatter intake during the T.congolense infection showed asmaller increase in urea and a higher increase in nonesterified fatty acids and B-hydroxy butyrate levels in theirblood.Evidence was obtained that the relative decrease in drymatter intake for individual goats during a T.vivax infectioncan be predicted on the basis of urea and creatinineresponses measured in the blood during a previous infectionwith T.congolense infection.

INTRODUCTIONStudies in various parts of West Africa have shown thattrypanotolerant breeds of cattle have a higher productivity thansusceptible breeds, even under a light tsetse challenge (4).Previous trials have shown that experimental infections withTvivax (3,12) resulted in reduced feed intake in West AfricanDwarf Goats, a breed considered to be trypanotolerant (1,4, 3,12).

Zwart et al. (15) found that the reduction in feed intake of WestAfrican Dwarf Goats infected with Tvivax was very individual.Infected animals could be divided into three groups; those thatmaintained their feed intake during infection (low responders),those that reduced their feed intake to a medium level (mediumresponders) and those that reduced their intake to very lowlevels (high responders). Reduction of feed intake results in a

Department of Tropical Animal Husbandry, Wageningen Agricultural University, POBox 338, 6700 AK Wageningen, the Netherlands.

Njala University College, Freetown, Sierra Leone.3 Department of Large Animal Medicine and Nutrition of Large Animals, University of

Utrecht, PO.Box 80152, 3508 TD Utrecht, the Netherlands.

Veterinary Quartely 1993; 15: 5-9

decrease of productivity. It is therefore worthwhile to study feedintake reduction in individual goats after experimental trypano-soma infections with Tcongolense and Tvivax and to checkwhether experimental infection with one trypanosoma has apredictor value for the outcome of an experimental infectionwith another type.One aim of the present study was to check whether, forindividual goats, changes in feed intake during a Tcongolenseinfection are of value for predicting changes in reaction in feedintake during a Tvivax infection. A second aim was toinvestigate to what extent different blood variables undergo thesame changes during a Tvivax infection as during aTcongelense infection. A third aim was to assess whetherchanges in blood variables are of value for predicting feed intakeduring a Tvivax infection.

MATERIALS AND METHODSAnimals and housingTwenty-three castrated male goats from a flock of West AfricanDwarf Goats were used. The flock was established about 12years ago at the Agricultural University in Wageningen and hasa minimal history of disease. At the start of the experiment theanimals were 15.5 ± 0.2 months old and weighed 22.8 ± 2.5 kg.The animals were allotted at random to two groups, 9 to a non-infected control group and 14 to an infected group. The goatswere housed in individual cages 12 days before the experimentstarted. After the first infection period, the animals were kept ingroups during a recovery period of 4 weeks. After that theanimals were placed on the balance crates again for the secondinfection period until the end of the trial. Light was on from 7.00to 19.00 h.

Experimental designThe experiment consisted of two periods, both containing a pre-infection and an infection period. Both pre-infection periodslasted 14 days, the first infection (Tcongolense) period 28 days,and the second infection (Tvivax) period 34 days (Table 1).During the first infection period the 14 goats from the infectedgroup were infected with a stabilate of Tcongolense strainEATRO 325 (11). This stabilate was first used to infect 10 mice.The goats were then infected intravenously by injecting 1 mlmouseblood containing 5 million trypanosomes.

5 T I I I V I I f R I N A R Y Q U A R T I R L Y , Vol. 1 5 N o 1 , MARCH.1 9 9 3

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