J.vet. Phunnacol. Therap. 13,356360,1990.
Pharmacokinetics and bioavailability of erythromycin in pigeons (Columba Zivia) E. VANHAECKE,* P. DE BACKER,t J. P. REMONS & L. A. DEVRIESEO Laboratories of *Pharmaceutical Microbiology and Hygiene and $Pharmaceutical Technology, State University of Ghent, Harelbekestraat 72, and §Faculty of Veterinary Medicine, Casinoplein 24, B-9000 Ghent, and toropharma, Bazelstraat 122, B-2760 Kruibeke, Belgium Vanhaecke, E.. De Backer, P.. Remon, J.P. & Devriese, L.A. Pharmacokinetics and bioavailability of erythromycin in pigeons (Columba livia).J. vet. Phannacol. Therap. 13, 356-360. Tissue and plasma concentrations were determined after intravenous and oral administration of erythromycin to pigeons to establish the pharmacokinetics and bioavailability of the drug. A short mean half-life of elimination of 0.9 h was found. The relative bioavailability after direct crop administration of erythromycin thiocyanate or erythromycin ethylsuccinate at a dosage rate of 100 mglkg was less than 10%. At a drug concentration in drinking water of 1 g/l, erythromycin plasma levels were barely detectable, whilst lung and trachea concentrations reached a maximum of 1.6 pg/ml. Even after crop administration of IOO-mg/kg erythromycin thiocyanate, low plasma levels were obtained, whilst lung and trachea concentrations were substantially higher. Prescribed drinkingwater regimens seemed unable to yield therapeutic tissue concentrations. Only individual crop administration seemed an appropriate medication method. The use of erythromycin ethylsuccinate did not present any advantage in comparison with erythromycin thiocyanate.
J . P . Remon, Laboratoly of Plrar?naceu~iccilTechnology, Slate University of Ghent, Harelbekestraat 72, 8-9000 Ghent, Belgium.
INTRODUCTION Erythromycin is a macrolide antibiotic active against most Gram-positive and some Gramnegative bacteria. Because erythromycin is degraded by the acid secreted in the stomach, modifications in chemical structure and in dosage form have been used to improve absorption. Erythromycin products for oral use are available as enteric-coated erythromycin base preparations, as an insoluble salt (erythromycin stearate) and as esters (erythromycin ethylsuccinate; erythromycin estolate; erythromycin thiocyanate). In veterinary practice, erythromycin is mainly used for the control of mycoplasmal and respiratory-tract infections (Sinclair, 1980;
356
Jordan et al., 1981; Macowan et al., 1981; Howse & Jordan, 1983; Reece el al., 1986). Although some reports are available on the pharmacology and bioavailability of macrolide antibiotics in poultry (Locke et al., 1982), information on erythromycin is lacking for pigeons (Columba livia). This study was undertaken to establish the pharmacokinetics and oral bioavailability of thiocyanate and ethylsuccinate esters of erythromycin in pigeons.
METHODS The three erythromycin formulations used in this study were: erythromycin thiocyanate
(Erythrocine-W@, Ceva N.V., Brussels, Belgium), available as a water-soluble powder containing the equivalent of 5 I-mg/g erythromycin base; erythromycin lactobionate containing the equivalent of 66-mg/g erythromycin basdg (Erythromycin I.V.@, Abbott Lab., Ottignies, Belgium) presented as a powder for reconstitution and erythromycin ethylsuccinate (Erythrocynee, Abbott Lab., Ottignies, Belgium), presented as a suspension containing 50-mg/ml erythromycin base. Pharmacokinetic and bioavailability experiments were performed on six homing pigeons, weighing 400 f 50 g. Pharmacokinetic data were obtained after a single intravenous injection in a wing vein (vena cutanea ulnaris) of erythromycin lactobionate at a dosage level of 20-mg/kg erythromycin base. A second group of six pigeons received erythromycin ethylsuccinate directly into the crop once at a dosage level of 20 mg/kg and after 2 weeks at a dosage rate of 1.00 mg/kg. Three weeks later the same pigeons were also used in a similar experiment using erythromycin thiocyanate at the same dose levels. In all experiments the pigeons were housed individually and had free access to water and a standard breeding mix until 12 h before drug administration. In another experiment drinking water was dosed with erythromycin thiocyanate at a level of 1 gfl erythromycin base. In this experiment the pigeons had free access to food and the medicated water. Blood samples were taken by venepuncture of the medial leg vein at 0, 0.5, 1, 2 , 4 and 6 h after i.v. administration and 0, 1, 2, 4 and 6 h after oral administration of the erythromycin esters. During the experiment with medicated drinking water, blood samples were taken at 0, 1, 2, 4, 8 and 24 h. In a final experiment, erythromycin thiocyanate was again administered into the crop at a dosage level of IOO-mg/kg erythromycin base (n = 6), after which the birds were killed either 2 h (n = 3) or 6 h (n = 3) after drug administration. In these pigeons antibiotic levels were determined in plasma, lung tissue and trachea. Erythromycin thiocyanate was administered to another six pigeons in their drinking water at a dosage level of I-gfl erythromycin base. After death, 24 h after drug administration via drinking water was started, plasma, lung tissue and trachea were
collected and drug concentrations determined. A11 blood samples were collected in heparinized glass tubes. Plasma, lung tissue and trachea were stored at -30°C pending analysis. A microbiological method, using an agarwell diffusion technique, was used to assay plasma and tissue samples for erythromycin. The organism used was Mitrococcur lutea (ATCC 934 1; American Type Culture Collection, Rockville, MD. USA). A quantity (20 or 30 ml) of antibiotic medium number 11 (Difco no. 593, Difco Detroit, MI, USA) was poured into standard plastic disposable Petri dishes (90 mm in diameter). Wells 2-6 mm in diameter were punched in the seeded agar and filled with 6 2 0 p1 of the unknown or standard solution. Trachea or lung tissue was crushed in a mortar, extracted with methanol and diluted in a phosphate buffer (pH 8.0) resulting in an extraction yield of 95.2 f 1.7% (n = 10). After growth at 25°C for 2 days, zone sizes were measured to an accuracy of 0.001 mm with a Mitutoyo optical comparator (Mitutoyo Ltd.. Tokyo, Japan). Six Petri dishes were used for each unknown sample and the results were calculated by the method of the least squares with use of the individual calibration curves for each of the six Petri dishes per unknown sample. Methanolic standard stock solutions (1000 pg/ml) were prepared from a powder of known potency (950 iu/mg, WHO, International Standard) and stored in liquid nitrogen. Working standards were prepared daily in antibiotic-free blank plasma or in the phosphate buffer (pH 8.0) for the erythromycin tissue determination (0.7 g of KH2P04, 12.2 g of K2HP04.2H20,water to 1 1). As blood contaminated trachea and tissue samples, the amount of blood in those preparations was determined by visual comparison with a standard series of pigeon blood in buffered saline. The total erythromycin activity in trachea and tissue samples was subsequently adjusted taking into account the estimated erythromycin activity. RESULTS The pharmacokinetics of erythromycin were
358 E. Vanhaah et al. determined after a single intravenous injection of erythromycin lactobionate into six pigeons. An elimination half-life of 54.0 +21.9 min, an apparent volume of distribution (V,) of 2.3 k 0.7 Vkg and a total b o d y clearance of 1.69 2 0.63 Vkg/h (n = 6) were calculated from the intravenous data. After administration into the crop of erythromycin ethylsuccinate or erythromycin thiocyanate, the mean oral bioavailability values were always less than lo%, irrespective of the doses. The average peak plasma concentration was 0.07 k 0.05 pg/ml after crop administration of 20 mg/kg erythromycin ethylsuccinate and 1.95 k 0.56 pg/ml after a dose of 100 mg/kg. After crop administration of 20-mgIkg and IOO-mg/kg erythromycin thiocyanate, mean respective peak plasma concentrations of 0.04 k 0.03 and 0.75 k 0.55 pg/ml were obtained. Following erythromycin-thiocyanate administration in drinking water (l-gA erythromycin base), it was almost impossible to detect any erythromycin in plasma over a 24-h period (Fig. 1). In comparison to the direct crop administration of 100 mg/kg, the relative bioavailability was only about 42%. T h e absolute bioavailability for the antibiotic in the drinking water was, however, less than 2%.
“1
T
I
-E
c
2
3
5
6
12 1
\
0,
C
0 .-c
e
c
c (D
0 C 0
.-0C
z
e
f 5,
L
w
4
3
2 I
0 Time ( h )
FIG. 1. Mean (k SD) plasma concentrations of erythromycin after single crop administrations of 100-mgkg erythromycin ethylsuccinate (8). or erythromycin thiocyanate at dosages of 20 mgikg ( 0 )or 100 mglkg (m). Plasma levels of erythromycin after drinking-water medication of I -g/l erythroare also shown. mycin thiocyanate (0)
7
8
9
10
II
12
Pigeon number
FIG. 2. Simultaneous lung (m), trachea tissue (St) and plasma (m) concentrations (mean k SD) of erythromycin (a) 2 and (b) 6 h after crop administrations of erythromycin thiocyanate at a dosage level of 100-mgikg erythromycin base and (c) 24 h after erythromycin administration in drinking water at a dosage level of 1-gfl erythromycin base.
Erythromycin in pigeons 359
T h e plasma, lung tissue and trachea antibiotic concentrations after crop administration of lOO-mg/kg erythromycin as erythromycin thiocyanate are shown in Fig. 2. T h e tissue concentrations were significantly higher than the plasma concentrations. Plasma levels vaned between 0.48 and 0.77 pg/ml 2 h after administration, while lung tissue and trachea antibiotic concentrations varied between 1.8 and 3.4 pg/ml. Six hours after the experiment was started, plasma levels were between 0.06 and 0.19 pg/ ml, while tissue concentrations varied between 0.7 and 11.3 pglml. When erythromycin thiocyanate was administered at a dose level of 1 g/l in drinking water, plasma concentrations were very low 24 h after administration. T h e lung tissue and trachea concentrations varied between 0.01 and 4.30 pg/ml. DISCUSSION Respiratory diseases are widespread in racing and fancy pigeons. Racing birds are, particularly during the racing season, through exhibitions and auctions, exposed to infections. Although the clinical efficacy of drinking water medicated with erythromycin is accepted by practitioners, no data were available on pharmacokinetics, bioavailability and tissue concentration for this antibiotic in this species. From the present results it is clear that the half-life of erythromycin in pigeons is short, even shorter than tylosin, a related antibiotic (Locke et al., 1982). The large volume of distribution indicated that a large amount of antibiotic was concentrated in the tissues. This was confirmed by comparison with the plasma concentration obtained after crop administration (lOO-mg/kg erythromycin). In some cases the ratio was 100-fold higher. These high tissue-plasma ratios were also obtained after erythromycin-thiocyanate administration in the drinking water. These findings are in agreement with those of other investigators who also reported low plasma levels of erythromycin in comparison to tissue concentrations in calves (Dvorak et al., 1979; Soback et al., 1987). In pigeons the relative bioavailability of
erythromycin after oral administration was also very low. From our data a lower bioavailability than that reported by Soback et al. (1987) in pre-ruminant calves was calculated. Devriese and Dutta (1984) administered erythromycin into the drinking water of chickens. They also found very low plasma levels of the antibiotic after oral administration in this species. They explained the low bioavailability by the activity of erythromycin degrading lactobacilli in the crop (Devriese & Dutta, 1984). In chickens and pigeons erythromycin plasma levels of less than 0.5 pg/ml were obtained after administration of the antibiotic in drinking water. As levels below 0.5 pg/ml are generally considered to be inactive, it is obvious that even with high doses in the drinking water (100 mgd) the antibiotic is not appropriate for the treatment of respiratory diseases in birds. Only by individual oral medication, directly into the crop at a high dosage level of 100 mg/kg, can therapeutic levels be reached. When this method of administration was used, no significant difference (Kruskal-Wallis test) in plasma drug levels was observed between erythromycin ethylsuccinate and erythromycin thiocyanate. From these data it is likely that plasma concentration-time profiles are an inappropriate method for the clinical evaluation of the use of erythromycin in pigeons. As erythromycin levels in the tissues remained well above bacteriostatic concentration, while those in plasma declined, antibiotic concentration in the infected tissues seems a more appropriate evaluation method.
REFERENCES Devriese, L.A. 8c Dutta, G.N. (1984) Effects of erythromycin-inactivating Lactobacillur crop flora on blood levels of erythromycin given orally to chicks. Journal of Veterinary Pharmacology and Therapeutics, 7, 49-53. Dvorak, M., Strakova, J. 8c Sevcik, B. (1979) Erythromycin inj. ad usum vet. pharmacokinetics in blood serum and organs. VeferinariaSpofa, 213, 67-74. Howse, J.N. &Jordan, F.T.W. (1983) Treatment of racing pigeons naturally infected with Mycoplama columborale and M . columbinum. Veterinary Record, 112, 324-326. Jordan, F.T.W., Howse. J.N., Adams, M.P. 8c
360 E. Vanhaecke et al. Fatunmbi. 0.0. (1981) The isolation of Myco-
p”(m columbinum and M . columborak from feral pigeons. Veterinury Record, 109, 450. Locke, D., Bush, M. & Carpenter, J.W. (1982) Pharmacokinetics and concentrations of tylosin in selected avian species. American J o u m l of Vefm’nary Research, 43. 1807-1810. Macowan, K.J., Jones, H.G.R., Randall, C.J. & Jordan, F.T.W. (1981) Myco$usma columborale in a respiratory condition of pigeons and experimental air sacculitis of chickens. V e h i n u v Record, 109, 562.
Reece. R.L., Ireland, L. & Scott, P.C. (1986) Mycoplasmosis in racing pigeons. Awfraliun Vefesnury Journal, 63, 166-167. Sinclair, D.V. (1980) Respiratory disease in pigeons. Veterinury Record, 106, 466. Soback, S., Ziv, G. & Kurtz, B. (1987) Agedependent oral bioavailability of erythromycin rhiocyanate in calves.Journal of Velm’nuryMedicine Series A, 24, 1Q2-107.
Pharmacokinetics and bioavailability of erythromycin in pigeons (Columba Zivia) E. VANHAECKE,* P. DE BACKER,t J. P. REMONS & L. A. DEVRIESEO Laboratories of *Pharmaceutical Microbiology and Hygiene and $Pharmaceutical Technology, State University of Ghent, Harelbekestraat 72, and §Faculty of Veterinary Medicine, Casinoplein 24, B-9000 Ghent, and toropharma, Bazelstraat 122, B-2760 Kruibeke, Belgium Vanhaecke, E.. De Backer, P.. Remon, J.P. & Devriese, L.A. Pharmacokinetics and bioavailability of erythromycin in pigeons (Columba livia).J. vet. Phannacol. Therap. 13, 356-360. Tissue and plasma concentrations were determined after intravenous and oral administration of erythromycin to pigeons to establish the pharmacokinetics and bioavailability of the drug. A short mean half-life of elimination of 0.9 h was found. The relative bioavailability after direct crop administration of erythromycin thiocyanate or erythromycin ethylsuccinate at a dosage rate of 100 mglkg was less than 10%. At a drug concentration in drinking water of 1 g/l, erythromycin plasma levels were barely detectable, whilst lung and trachea concentrations reached a maximum of 1.6 pg/ml. Even after crop administration of IOO-mg/kg erythromycin thiocyanate, low plasma levels were obtained, whilst lung and trachea concentrations were substantially higher. Prescribed drinkingwater regimens seemed unable to yield therapeutic tissue concentrations. Only individual crop administration seemed an appropriate medication method. The use of erythromycin ethylsuccinate did not present any advantage in comparison with erythromycin thiocyanate.
J . P . Remon, Laboratoly of Plrar?naceu~iccilTechnology, Slate University of Ghent, Harelbekestraat 72, 8-9000 Ghent, Belgium.
INTRODUCTION Erythromycin is a macrolide antibiotic active against most Gram-positive and some Gramnegative bacteria. Because erythromycin is degraded by the acid secreted in the stomach, modifications in chemical structure and in dosage form have been used to improve absorption. Erythromycin products for oral use are available as enteric-coated erythromycin base preparations, as an insoluble salt (erythromycin stearate) and as esters (erythromycin ethylsuccinate; erythromycin estolate; erythromycin thiocyanate). In veterinary practice, erythromycin is mainly used for the control of mycoplasmal and respiratory-tract infections (Sinclair, 1980;
356
Jordan et al., 1981; Macowan et al., 1981; Howse & Jordan, 1983; Reece el al., 1986). Although some reports are available on the pharmacology and bioavailability of macrolide antibiotics in poultry (Locke et al., 1982), information on erythromycin is lacking for pigeons (Columba livia). This study was undertaken to establish the pharmacokinetics and oral bioavailability of thiocyanate and ethylsuccinate esters of erythromycin in pigeons.
METHODS The three erythromycin formulations used in this study were: erythromycin thiocyanate
(Erythrocine-W@, Ceva N.V., Brussels, Belgium), available as a water-soluble powder containing the equivalent of 5 I-mg/g erythromycin base; erythromycin lactobionate containing the equivalent of 66-mg/g erythromycin basdg (Erythromycin I.V.@, Abbott Lab., Ottignies, Belgium) presented as a powder for reconstitution and erythromycin ethylsuccinate (Erythrocynee, Abbott Lab., Ottignies, Belgium), presented as a suspension containing 50-mg/ml erythromycin base. Pharmacokinetic and bioavailability experiments were performed on six homing pigeons, weighing 400 f 50 g. Pharmacokinetic data were obtained after a single intravenous injection in a wing vein (vena cutanea ulnaris) of erythromycin lactobionate at a dosage level of 20-mg/kg erythromycin base. A second group of six pigeons received erythromycin ethylsuccinate directly into the crop once at a dosage level of 20 mg/kg and after 2 weeks at a dosage rate of 1.00 mg/kg. Three weeks later the same pigeons were also used in a similar experiment using erythromycin thiocyanate at the same dose levels. In all experiments the pigeons were housed individually and had free access to water and a standard breeding mix until 12 h before drug administration. In another experiment drinking water was dosed with erythromycin thiocyanate at a level of 1 gfl erythromycin base. In this experiment the pigeons had free access to food and the medicated water. Blood samples were taken by venepuncture of the medial leg vein at 0, 0.5, 1, 2 , 4 and 6 h after i.v. administration and 0, 1, 2, 4 and 6 h after oral administration of the erythromycin esters. During the experiment with medicated drinking water, blood samples were taken at 0, 1, 2, 4, 8 and 24 h. In a final experiment, erythromycin thiocyanate was again administered into the crop at a dosage level of IOO-mg/kg erythromycin base (n = 6), after which the birds were killed either 2 h (n = 3) or 6 h (n = 3) after drug administration. In these pigeons antibiotic levels were determined in plasma, lung tissue and trachea. Erythromycin thiocyanate was administered to another six pigeons in their drinking water at a dosage level of I-gfl erythromycin base. After death, 24 h after drug administration via drinking water was started, plasma, lung tissue and trachea were
collected and drug concentrations determined. A11 blood samples were collected in heparinized glass tubes. Plasma, lung tissue and trachea were stored at -30°C pending analysis. A microbiological method, using an agarwell diffusion technique, was used to assay plasma and tissue samples for erythromycin. The organism used was Mitrococcur lutea (ATCC 934 1; American Type Culture Collection, Rockville, MD. USA). A quantity (20 or 30 ml) of antibiotic medium number 11 (Difco no. 593, Difco Detroit, MI, USA) was poured into standard plastic disposable Petri dishes (90 mm in diameter). Wells 2-6 mm in diameter were punched in the seeded agar and filled with 6 2 0 p1 of the unknown or standard solution. Trachea or lung tissue was crushed in a mortar, extracted with methanol and diluted in a phosphate buffer (pH 8.0) resulting in an extraction yield of 95.2 f 1.7% (n = 10). After growth at 25°C for 2 days, zone sizes were measured to an accuracy of 0.001 mm with a Mitutoyo optical comparator (Mitutoyo Ltd.. Tokyo, Japan). Six Petri dishes were used for each unknown sample and the results were calculated by the method of the least squares with use of the individual calibration curves for each of the six Petri dishes per unknown sample. Methanolic standard stock solutions (1000 pg/ml) were prepared from a powder of known potency (950 iu/mg, WHO, International Standard) and stored in liquid nitrogen. Working standards were prepared daily in antibiotic-free blank plasma or in the phosphate buffer (pH 8.0) for the erythromycin tissue determination (0.7 g of KH2P04, 12.2 g of K2HP04.2H20,water to 1 1). As blood contaminated trachea and tissue samples, the amount of blood in those preparations was determined by visual comparison with a standard series of pigeon blood in buffered saline. The total erythromycin activity in trachea and tissue samples was subsequently adjusted taking into account the estimated erythromycin activity. RESULTS The pharmacokinetics of erythromycin were
358 E. Vanhaah et al. determined after a single intravenous injection of erythromycin lactobionate into six pigeons. An elimination half-life of 54.0 +21.9 min, an apparent volume of distribution (V,) of 2.3 k 0.7 Vkg and a total b o d y clearance of 1.69 2 0.63 Vkg/h (n = 6) were calculated from the intravenous data. After administration into the crop of erythromycin ethylsuccinate or erythromycin thiocyanate, the mean oral bioavailability values were always less than lo%, irrespective of the doses. The average peak plasma concentration was 0.07 k 0.05 pg/ml after crop administration of 20 mg/kg erythromycin ethylsuccinate and 1.95 k 0.56 pg/ml after a dose of 100 mg/kg. After crop administration of 20-mgIkg and IOO-mg/kg erythromycin thiocyanate, mean respective peak plasma concentrations of 0.04 k 0.03 and 0.75 k 0.55 pg/ml were obtained. Following erythromycin-thiocyanate administration in drinking water (l-gA erythromycin base), it was almost impossible to detect any erythromycin in plasma over a 24-h period (Fig. 1). In comparison to the direct crop administration of 100 mg/kg, the relative bioavailability was only about 42%. T h e absolute bioavailability for the antibiotic in the drinking water was, however, less than 2%.
“1
T
I
-E
c
2
3
5
6
12 1
\
0,
C
0 .-c
e
c
c (D
0 C 0
.-0C
z
e
f 5,
L
w
4
3
2 I
0 Time ( h )
FIG. 1. Mean (k SD) plasma concentrations of erythromycin after single crop administrations of 100-mgkg erythromycin ethylsuccinate (8). or erythromycin thiocyanate at dosages of 20 mgikg ( 0 )or 100 mglkg (m). Plasma levels of erythromycin after drinking-water medication of I -g/l erythroare also shown. mycin thiocyanate (0)
7
8
9
10
II
12
Pigeon number
FIG. 2. Simultaneous lung (m), trachea tissue (St) and plasma (m) concentrations (mean k SD) of erythromycin (a) 2 and (b) 6 h after crop administrations of erythromycin thiocyanate at a dosage level of 100-mgikg erythromycin base and (c) 24 h after erythromycin administration in drinking water at a dosage level of 1-gfl erythromycin base.
Erythromycin in pigeons 359
T h e plasma, lung tissue and trachea antibiotic concentrations after crop administration of lOO-mg/kg erythromycin as erythromycin thiocyanate are shown in Fig. 2. T h e tissue concentrations were significantly higher than the plasma concentrations. Plasma levels vaned between 0.48 and 0.77 pg/ml 2 h after administration, while lung tissue and trachea antibiotic concentrations varied between 1.8 and 3.4 pg/ml. Six hours after the experiment was started, plasma levels were between 0.06 and 0.19 pg/ ml, while tissue concentrations varied between 0.7 and 11.3 pglml. When erythromycin thiocyanate was administered at a dose level of 1 g/l in drinking water, plasma concentrations were very low 24 h after administration. T h e lung tissue and trachea concentrations varied between 0.01 and 4.30 pg/ml. DISCUSSION Respiratory diseases are widespread in racing and fancy pigeons. Racing birds are, particularly during the racing season, through exhibitions and auctions, exposed to infections. Although the clinical efficacy of drinking water medicated with erythromycin is accepted by practitioners, no data were available on pharmacokinetics, bioavailability and tissue concentration for this antibiotic in this species. From the present results it is clear that the half-life of erythromycin in pigeons is short, even shorter than tylosin, a related antibiotic (Locke et al., 1982). The large volume of distribution indicated that a large amount of antibiotic was concentrated in the tissues. This was confirmed by comparison with the plasma concentration obtained after crop administration (lOO-mg/kg erythromycin). In some cases the ratio was 100-fold higher. These high tissue-plasma ratios were also obtained after erythromycin-thiocyanate administration in the drinking water. These findings are in agreement with those of other investigators who also reported low plasma levels of erythromycin in comparison to tissue concentrations in calves (Dvorak et al., 1979; Soback et al., 1987). In pigeons the relative bioavailability of
erythromycin after oral administration was also very low. From our data a lower bioavailability than that reported by Soback et al. (1987) in pre-ruminant calves was calculated. Devriese and Dutta (1984) administered erythromycin into the drinking water of chickens. They also found very low plasma levels of the antibiotic after oral administration in this species. They explained the low bioavailability by the activity of erythromycin degrading lactobacilli in the crop (Devriese & Dutta, 1984). In chickens and pigeons erythromycin plasma levels of less than 0.5 pg/ml were obtained after administration of the antibiotic in drinking water. As levels below 0.5 pg/ml are generally considered to be inactive, it is obvious that even with high doses in the drinking water (100 mgd) the antibiotic is not appropriate for the treatment of respiratory diseases in birds. Only by individual oral medication, directly into the crop at a high dosage level of 100 mg/kg, can therapeutic levels be reached. When this method of administration was used, no significant difference (Kruskal-Wallis test) in plasma drug levels was observed between erythromycin ethylsuccinate and erythromycin thiocyanate. From these data it is likely that plasma concentration-time profiles are an inappropriate method for the clinical evaluation of the use of erythromycin in pigeons. As erythromycin levels in the tissues remained well above bacteriostatic concentration, while those in plasma declined, antibiotic concentration in the infected tissues seems a more appropriate evaluation method.
REFERENCES Devriese, L.A. 8c Dutta, G.N. (1984) Effects of erythromycin-inactivating Lactobacillur crop flora on blood levels of erythromycin given orally to chicks. Journal of Veterinary Pharmacology and Therapeutics, 7, 49-53. Dvorak, M., Strakova, J. 8c Sevcik, B. (1979) Erythromycin inj. ad usum vet. pharmacokinetics in blood serum and organs. VeferinariaSpofa, 213, 67-74. Howse, J.N. &Jordan, F.T.W. (1983) Treatment of racing pigeons naturally infected with Mycoplama columborale and M . columbinum. Veterinary Record, 112, 324-326. Jordan, F.T.W., Howse. J.N., Adams, M.P. 8c
360 E. Vanhaecke et al. Fatunmbi. 0.0. (1981) The isolation of Myco-
p”(m columbinum and M . columborak from feral pigeons. Veterinury Record, 109, 450. Locke, D., Bush, M. & Carpenter, J.W. (1982) Pharmacokinetics and concentrations of tylosin in selected avian species. American J o u m l of Vefm’nary Research, 43. 1807-1810. Macowan, K.J., Jones, H.G.R., Randall, C.J. & Jordan, F.T.W. (1981) Myco$usma columborale in a respiratory condition of pigeons and experimental air sacculitis of chickens. V e h i n u v Record, 109, 562.
Reece. R.L., Ireland, L. & Scott, P.C. (1986) Mycoplasmosis in racing pigeons. Awfraliun Vefesnury Journal, 63, 166-167. Sinclair, D.V. (1980) Respiratory disease in pigeons. Veterinury Record, 106, 466. Soback, S., Ziv, G. & Kurtz, B. (1987) Agedependent oral bioavailability of erythromycin rhiocyanate in calves.Journal of Velm’nuryMedicine Series A, 24, 1Q2-107.
