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Sulfamerazine and Sulfamethazine Blood Levels in Turkeys*
Sulfamerazine and Sulfamethazine Blood Levels in Turkeys* S T E P H E N G O R D E U K , J R . AND M A R I O N L E A R N E D
State College, Perm. (Received for publication October 30. 19.47)
W
HEN therapeutic doses of sulfamerazine for cecal coccidiosis in chickens were determined the question arose as to whether or not such doses were favorable for turkeys poults. Consequently, blood level studies were made during the administration of varying dosages of sulfamerazine and sulfamethazine to young turkey poults. Thorp el al. (1947) reported some blood levels of free sulfamerazine in chickens in a paper on the chemotherapy of cecal coccidiosis. Sodium sulfamerazine administered in a concentration of 0.2 percent in water for five days resulted in an average blood concentration of 13.68 mg. of free sulfamerazine per 100 ml. The feeding of a 1.0 percent sulfamerazine mash gave an average blood level of 27.68 mg. of free drug per 100 ml. of blood while a 0.25 percent concentration of sulfamerazine in mash resulted in an average of 8.26 mg. of free drug per 100 ml. of blood during a five-day treatment. Gordeuk, Learned and Thorp (1947) later reported the average concentrations of sulfamethazine, chlorodiazirie and sulfaguanidine in the blood of chickens. A 0.4 * Authorized for publication October 27,1947, as paper No. 1399 in the journal series of The Pennsylvania Agricultural Experiment Station from the Animal Pathology Laboratory of the Department of Animal Husbandry. This work was supported in part by research grants from Sharp & Dohme, Glenolden, Pennsylvania and Lederle Laboratories, Pearl River, New York.
percent sulfamethazine mash fed to chicks resulted in an average blood concentration of 14.55 mg. of free drug per 100 ml. during a three-day treatment. The administration of 0.15 percent chlorodiazine in mash resulted in an average concentration of 8.00 mg. of free drug per 100 ml. of blood. Giving 1.0 percent sulfaguanidine and cerelose (50 percent of each) to chicks in the drinking water resulted in a blood concentration of 4.50 mg. of free sulfaguanidine per 100 ml. while the feeding of a 1.0 percent sulfaguanidine mash gave a blood level of 7.57 mg. of free drug per 100 ml. of blood. EXPERIMENTAL PROCEDURE
White Holland turkey poults were supplied by the Department of Poultry Husbandry of The Pennsylvania State College at one day of age. The poults used for sulfamerazine blood level determinations were hatched on February 10, 1947. They were kept in electrically heated batteries and fed regular turkey poult mash. These poults were inoculated with Eimeria tenella oocysts on March 10, and treated on March 15, 16, 17, 18 and 19. Blood samples were drawn on March 17, 18, 19 and 20 when the poults were approximately five weeks old. The treatment was repeated from April 8 to 15 when the turkey poults were eight weeks old and blood samples were secured on April 9, 10 and 11. The poults were autopsied on April 22 and examined for 329
330
STEPHEN GORDEUK, JR. AND MARION LEARNED
gross visceral pathology. The poults used for the determination of blood concentrations of sulfamethazine were hatched on March 24, 1947 and received the first treatment on April 20, 21, 22 and 23. Blood samples were secured from four poults in each treated group on April 21, 22, 23 and 24. These poults were not inoculated with coccidia. The treatment was repeated on May 25, 26, 27 and 28 when the poults were nine weeks old. Blood samples were taken on May 26, 27, 28 and 29. The poults were autopsied on June 10 and examined for possible gross visceral lesions. The blood concentrations of sulfamerazine and sulfamethazine were determined by Frank M. Singer of the Agricultural and Biological Chemistry Department employing the method of Bratton and . Marshall. Following is a brief outline of the experiments: Sulfamerazine Experiment 1—Five-week-old poults.* Pen 1—0.2 percent Sodium sulfamerazine in water. Pen 2—0.1 percent Sodium sulfamerazine in water. Pen 3—0.5 percent Sulfamerazine in mash. Pen 4—Untreated uninoculated control. Pen 5—Untreated inoculated control. * Poults in pens 1, 2, 3 and 5 received oral inoculations of infective Eimeria tenella oocysts. Sulfamerazine Experiment 2—Eight-week-old poults. Pen 1—0.2 percent Sodium sulfamerazine in water. Pen 2—0.1 percent Sodium sulfamerazine in water. Pen 3—0.5 percent Sulfamerazine in mash. Pen 4—Untreated control. Pen 5—0.25 percent Sulfamerazine in mash. Sulfamethazine Experiment 1—Four-week-old poults. Pen 1—0.2 percent Sodium sulfamethazine in water.
* All of the poults used from April 21 through 24 did not survive, making it necessary to make substitutions for the repeated study in May. Four in each treated pen were used.
Pen 2—0.1 percent Sodium sulfamethazine in water. Pen 3—0.4 percent Sulfamethazine in mash. Pen 4—Untreated controls. Sulfamethazine Experiment 2—Nine-week-old poults.* Pen 1—0.2 percent Sodium sulfamethazine in water. Pen 2—0.1 percent Sodium sulfamethazine in water. Pen 3—0.4 percent Sulfamethazine in mash. Pen 4—Untreated controls. DISCUSSION
Concentrations of 0.2 percent sodium sulfamerazine in water and 0.5 percent sulfamerazine in mash administered to five-week-old turkey poults resulted in comparable blood levels of free sulfamerazine, ranging from 18.9 to 24.2 mg. per 100 ml. of blood. The average blood levels of free sulfamerazine in the poults from the group receiving 0.1 percent sodium sulfamerazine in water were 9.4 to 10.6 mg. per 100 ml. Traces of conjugated drug were found in each group. Twenty-four hours after the discontinuance of treatment only faint traces of the drug were found in the groups receiving the higher dosages. (See Table 1.) When these poults were eight weeks old they were used again for further sulfamerazine blood level studies. This time four groups were treated and blood samples were drawn for three days during treatment. Birds in the additional experimental pen received 0.25 percent sulfamerazine in the mash. The poults receiving 0.5 percent sulfamerazine in the mash showed blood concentrations of the free drug similar to those obtained at the earlier age. The group of poults receiving 0.1 percent sodium sulfamerazine in water also maintained blood concentrations of free sulfamerazine that were quite comparable to the earlier findings but the blood levels of the free drug were somewhat lower in the group of
331
SULFAMERAZINE AND SULFAMETHAZINE BLOOD LEVELS IN TURKEYS TABLE 1.—Average blood levels of sulfamerazine in five-week-old turkey poults*
Days
4t
Mgs. per 100 ml. of blood
Mgs. per 100 ml. of blood
Mgs. per 100 ml. of blood
Free Drug
Total Drug
Conjugated Drug
0 . 2 % Sodium Sulfamerazine in water 0 . 1 % Sodium Sulfamerazine in water 0 . 5 % Sulfamerazine in mash
22.3 9.4 21.9
23.1 9.8 22.6
0.8 0.4 0.7
0 . 2 % Sodium Sulfamerazine in water 0 . 1 % Sodium Sulfamerazine in water 0 . 5 % Sulfamerazine in mash
21.8 10.6 24.2
22.4 11.1 25.1
0.6 0.6 0.9
0 . 2 % Sodium Sulfamerazine in water 0 . 1 % Sodium Sulfamerazine in water 0 . 5 % Sulfamerazine in mash
18.9 9.5 22.4
19.5 10.0 23.2
0.7 0.5 0.8
0 . 2 % Sodium Sulfamerazine in water 0 . 1 % Sodium Sulfamerazine in water 0 . 5 % Sulfamerazine in mash
0.1 0.0 0.1
0.1 0.0 0.1
0.0 0.0 0.0
Dosage
* The results represent the averages of four poults, t No .treatment 24 hours previous to bleeding.
poults receiving 0.2 percent sodium sulfamerazine in water. The administration of 0.1 percent sodium sulfamerazine in water and 0.25 percent sulfamerazine in mash gave relatively similar blood levels of the free drug. (See Table 2.) The administration of 0.2 percent sodium sulfamethazine to four-week-old turkey poults gave blood levels of free sulfa-
methazine that compared favorably with the levels of sulfamerazine attained in five-week-old turkey poults. From 19.0 to 21.2 mg. of free sulfamethazine were found in 100 ml. of blood. The amount of the free drug in the blood of poults receiving 0.4 percent sulfamethazine in mash was lower, ranging from 13.7 to 14.9 mg. per 100 ml. The use of 0.1 percent sodium
TABLE 2.—Average blood levels of sulfamerazine in eight-week-old turkey poults*
Days
Mgs. per 100 ml. of blood
Mgs. per 100 ml. of blood
Mgs. per 1C0 ml. of blood
Free Drug
Total Drug
Conjugated Drug
0 . 2 % Sodium Sulfamerazine in water 0 . 1 % Sodium Sulfamerazine in water 0 . 5 % Sulfamerazine in mash 0 . 2 5 % Sulfamerazine in mash
13.2 9.3 22.4 9.6
14.2 9.5 23.0 9.7
0.3 0.2 0.6 0.2
0 . 2 % Sodium Sulfamerazine in water 0.17% Sodium Sulfamerazine in water 0 . 5 % Sulfamerazine in mash 0 . 2 5 % Sulfamerazine in mash
18.2 9.9 24.3 8.9
19.1 10.4 25.1 9.4
0.9 0.5 0.8 0.5
0 . 2 % Sodium Sulfamerazine in water 0 . 1 % Sodium Sulfamerazine in water 0 . 5 % Sulfamerazine in mash 0 . 2 5 % Sulfamerazine in mash
17.8 9.7 24.1 7.8
18.4 10.0 24.8 7.9
0.5 0.4 0.7 0.1
Dosage
* The results represent the averages of four poults.
332
STEPHEN GORDETJK, J R . AND MARION LEARNED
TABLE 3.—Average blood levels of sulfamethazine in four-week-old turkey poults*
Days
4
t
Mgs. per 100 ml. of blood
Mgs. per 100 ml. of blood
Mgs. per 100 ml. of blood
Free Drug
Total Drugs
Conjugated Drug
0.2% Sodium Sulfamerazine in water 0.1% Sodium Sulfamerazine in water 0.4% Sulfamethazine in mash
21.2 11.9 14.9
23.9 13.4 16.6
3.2 1.5 1.7
0.2% Sodium Sulfamethazine in water 0.1% Sodium Sulfamethazine in water 0.4% Sulfamethazine in mash
19.0 12.4 14.7
22.2 13.9 16.0
3.2 1.5 1.3
0.2% Sodium Sulfamethazine in water 0.1% Sodium Sulfamethazine in water 0.4% Sulfamethazine in mash
21.2 10.6 13.7
24.4 12.0 15.3
3.2 1.4 1.6
0.2% Sodium Sulfamethazine in water 0.1% Sodium Sulfamethazine in water 0.4% Sulfamethazine in mash
1.1 0.6 0.6
1.2 0.7 0.7
0.1 0.1 0.1
Dosage
* The results represent the averages of four poults, t No treatment 24 hours previous to bleeding. sulfamethazine in drinking water produced blood levels ranging from 10.6 to 12.4 mg. per 100 ml. of blood. Insignificant amounts of sulfamethazine were detected in the blood 24 hours after the discontinuance of treatment. More sulfamethazine appeared in the blood in the conjugated form than
was the case with sulfamerazine. (See Table 3.) Table 4 presents similar data for the poults at the age of nine weeks. The administration of 0.2 percent sodium sulfamethazine in water at this age resulted in blood levels of the free drug that were considerably lower than those
TABLE 4.—Average blood levels of sulfamethazine in nine-week-old turkey poults* Mgs. per 100 ml. of blood
Mgs. per 100 ml. of blood
Mgs. per 1C0 ml. of blood
Free Drug
Total Drug
Conjugated Drug
0.2% Sodium Sulfamethazine in water 0.1% Sodium Sulfamethazine in water 0.4% Sulfamethazine in mash
9.0 8.3 16.6
11.4 10.0 19.4
2.4 1.7 2.8
0.2% Sodium Sulfamethazine in water 0 . 1 % Sodium Sulfamethazine in water 0.4% Sulfamethazine in mash
10.1 8.0 16.6
12.4 10.5 19.4
2.2 2.5 2.7
0.2% Sodium Sulfamethazine in water 0.1% Sodium Sulfamethazine in wtaer 0.4% Sulfamethazine in mash
11.0 7.0 16.7
13.2 8.2 18.5
2.3 1.2 1.8
0.2% Sodium Sulfamethazine in water 0.1% Sodium Sulfamethazine in water 0.4% Sulfamethazine in mash
1.0 0.5 1.1
1.2 0.6 1.5
0.2 0.1 0.3
Days
4t
* The results represent the average of four poults. f No treatment 24 hours previous to sampling.
SULFAMERAZINE AND SULFAMETHAZINE BLOOD LEVELS IN TURKEYS
found at the earlier age. The concentrations of free sulfamethazine at the other levels of treatment (0.1 percent sodium sulfamethazine in water and 0.4 percent sulfamethazine in mash) varied only a little from the previous determinations. Again, only trace amounts of free sulfamethazine were present in the blood of the poults 24 hours after the cessation of treatment. During the course of each study the poults received either medicated drinking water or mash ad libitum. The higher dosages of these sulfonamides given both in the water and in the mash resulted in higher blood concentrations of free drug. Before definite recommendations can be made in regard to proper dosages of these drugs for turkey poults more work should be done in which these sulfonamides are used experimentally as therapeutic agents. Inoculation of four-w'eek-old turkey poults with Eimeria tenella oocysts did not produce any lesions in the ceca or in any other portion of the intestine, demonstrating that this protozoan is not readily introduced into turkeys. No significant pathological changes were observed on post mortem examination of all poults used in the experiment. SUMMARY
1. Average blood concentrations of sulfamerazine in five-week-old turkey poults: 0.2 per cent Sodium sulfamerazine in water— 18.9 to 22.3 mg. per 100 ml. of blood of free drug. 0.1 per cent Sodium sulfamerazine in water—9.4 to 10.6 mg. per 100 ml. of blood of free drug.
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0.5 per cent Sulfamerazine in mash—21.9 to 24.2 mg. per 100 ml. of blood of free drug.
Average blood concentrations of sulfamerazine in eight-week-old turkey poults: 0.2 per cent Sodium sulfamerazine in water— 13.2 to 18.2 mg. per 100 ml. of blood of free drug. 0.1 per cent Sodium sulfamerazine in water—9.3 to 9.9 mg. per 100 ml. of blood of free drug. 0.5 per cent Sulfamerazine in mash—22.4 to 24.3 mg. per 100 ml. of blood of free drug. 0.25 per cent Sulfamerazine in mash—7.8 to 9.6 mg. Der 100 ml. of blood of free drug.
2. Average blood concentrations of sulfamethazine in four-week-old turkey poults: 0.2 per cent Sodium sulfamethazine in water— 19.0 to 21.2 mg. per 100 ml. of blood of free drug. 0.1 per cent Sodium sulfamethazine in water— 10.6 to 12.4 mg, per 100 ml. of blood of free drug. 0.4 per Cent Sulfamethazine in mash—13.7 to 14.9 mg. per 100 ml. of blood of free drug. Average blood concentrations of sulfamethazine in nine-week-old turkey poults: 0.2 per cent Sodium sulfamethazine in water— 9.0 to 11.0 mg. per 100 ml. of blood of free drug. 0.1 per cent Sodium sulfamethazine in water— 7.0 to 8.3 mg. per 100 ml. of blood of free drug. 0.4 per cent Sulfamethazine in mash—16.6 to 16.7 mg. per 100 ml. of blood of free drug. REFERENCES
Gordeuk, S., Jr., Learned, Marion, and Thorp, W. T. S., Observations on the Chemotherapy of Cecal Coccidiosis, Veterinary Medicine, 42, (1947): 223-228. Thorp, W. T. S., Gordeuk, S. Jr., Glantz, P. J. and Learned, Marion. The Chemotherapy of Cecal Coccidiosis, American Journal of Veterinary Research, 8, (1947): 196-203.
State College, Perm. (Received for publication October 30. 19.47)
W
HEN therapeutic doses of sulfamerazine for cecal coccidiosis in chickens were determined the question arose as to whether or not such doses were favorable for turkeys poults. Consequently, blood level studies were made during the administration of varying dosages of sulfamerazine and sulfamethazine to young turkey poults. Thorp el al. (1947) reported some blood levels of free sulfamerazine in chickens in a paper on the chemotherapy of cecal coccidiosis. Sodium sulfamerazine administered in a concentration of 0.2 percent in water for five days resulted in an average blood concentration of 13.68 mg. of free sulfamerazine per 100 ml. The feeding of a 1.0 percent sulfamerazine mash gave an average blood level of 27.68 mg. of free drug per 100 ml. of blood while a 0.25 percent concentration of sulfamerazine in mash resulted in an average of 8.26 mg. of free drug per 100 ml. of blood during a five-day treatment. Gordeuk, Learned and Thorp (1947) later reported the average concentrations of sulfamethazine, chlorodiazirie and sulfaguanidine in the blood of chickens. A 0.4 * Authorized for publication October 27,1947, as paper No. 1399 in the journal series of The Pennsylvania Agricultural Experiment Station from the Animal Pathology Laboratory of the Department of Animal Husbandry. This work was supported in part by research grants from Sharp & Dohme, Glenolden, Pennsylvania and Lederle Laboratories, Pearl River, New York.
percent sulfamethazine mash fed to chicks resulted in an average blood concentration of 14.55 mg. of free drug per 100 ml. during a three-day treatment. The administration of 0.15 percent chlorodiazine in mash resulted in an average concentration of 8.00 mg. of free drug per 100 ml. of blood. Giving 1.0 percent sulfaguanidine and cerelose (50 percent of each) to chicks in the drinking water resulted in a blood concentration of 4.50 mg. of free sulfaguanidine per 100 ml. while the feeding of a 1.0 percent sulfaguanidine mash gave a blood level of 7.57 mg. of free drug per 100 ml. of blood. EXPERIMENTAL PROCEDURE
White Holland turkey poults were supplied by the Department of Poultry Husbandry of The Pennsylvania State College at one day of age. The poults used for sulfamerazine blood level determinations were hatched on February 10, 1947. They were kept in electrically heated batteries and fed regular turkey poult mash. These poults were inoculated with Eimeria tenella oocysts on March 10, and treated on March 15, 16, 17, 18 and 19. Blood samples were drawn on March 17, 18, 19 and 20 when the poults were approximately five weeks old. The treatment was repeated from April 8 to 15 when the turkey poults were eight weeks old and blood samples were secured on April 9, 10 and 11. The poults were autopsied on April 22 and examined for 329
330
STEPHEN GORDEUK, JR. AND MARION LEARNED
gross visceral pathology. The poults used for the determination of blood concentrations of sulfamethazine were hatched on March 24, 1947 and received the first treatment on April 20, 21, 22 and 23. Blood samples were secured from four poults in each treated group on April 21, 22, 23 and 24. These poults were not inoculated with coccidia. The treatment was repeated on May 25, 26, 27 and 28 when the poults were nine weeks old. Blood samples were taken on May 26, 27, 28 and 29. The poults were autopsied on June 10 and examined for possible gross visceral lesions. The blood concentrations of sulfamerazine and sulfamethazine were determined by Frank M. Singer of the Agricultural and Biological Chemistry Department employing the method of Bratton and . Marshall. Following is a brief outline of the experiments: Sulfamerazine Experiment 1—Five-week-old poults.* Pen 1—0.2 percent Sodium sulfamerazine in water. Pen 2—0.1 percent Sodium sulfamerazine in water. Pen 3—0.5 percent Sulfamerazine in mash. Pen 4—Untreated uninoculated control. Pen 5—Untreated inoculated control. * Poults in pens 1, 2, 3 and 5 received oral inoculations of infective Eimeria tenella oocysts. Sulfamerazine Experiment 2—Eight-week-old poults. Pen 1—0.2 percent Sodium sulfamerazine in water. Pen 2—0.1 percent Sodium sulfamerazine in water. Pen 3—0.5 percent Sulfamerazine in mash. Pen 4—Untreated control. Pen 5—0.25 percent Sulfamerazine in mash. Sulfamethazine Experiment 1—Four-week-old poults. Pen 1—0.2 percent Sodium sulfamethazine in water.
* All of the poults used from April 21 through 24 did not survive, making it necessary to make substitutions for the repeated study in May. Four in each treated pen were used.
Pen 2—0.1 percent Sodium sulfamethazine in water. Pen 3—0.4 percent Sulfamethazine in mash. Pen 4—Untreated controls. Sulfamethazine Experiment 2—Nine-week-old poults.* Pen 1—0.2 percent Sodium sulfamethazine in water. Pen 2—0.1 percent Sodium sulfamethazine in water. Pen 3—0.4 percent Sulfamethazine in mash. Pen 4—Untreated controls. DISCUSSION
Concentrations of 0.2 percent sodium sulfamerazine in water and 0.5 percent sulfamerazine in mash administered to five-week-old turkey poults resulted in comparable blood levels of free sulfamerazine, ranging from 18.9 to 24.2 mg. per 100 ml. of blood. The average blood levels of free sulfamerazine in the poults from the group receiving 0.1 percent sodium sulfamerazine in water were 9.4 to 10.6 mg. per 100 ml. Traces of conjugated drug were found in each group. Twenty-four hours after the discontinuance of treatment only faint traces of the drug were found in the groups receiving the higher dosages. (See Table 1.) When these poults were eight weeks old they were used again for further sulfamerazine blood level studies. This time four groups were treated and blood samples were drawn for three days during treatment. Birds in the additional experimental pen received 0.25 percent sulfamerazine in the mash. The poults receiving 0.5 percent sulfamerazine in the mash showed blood concentrations of the free drug similar to those obtained at the earlier age. The group of poults receiving 0.1 percent sodium sulfamerazine in water also maintained blood concentrations of free sulfamerazine that were quite comparable to the earlier findings but the blood levels of the free drug were somewhat lower in the group of
331
SULFAMERAZINE AND SULFAMETHAZINE BLOOD LEVELS IN TURKEYS TABLE 1.—Average blood levels of sulfamerazine in five-week-old turkey poults*
Days
4t
Mgs. per 100 ml. of blood
Mgs. per 100 ml. of blood
Mgs. per 100 ml. of blood
Free Drug
Total Drug
Conjugated Drug
0 . 2 % Sodium Sulfamerazine in water 0 . 1 % Sodium Sulfamerazine in water 0 . 5 % Sulfamerazine in mash
22.3 9.4 21.9
23.1 9.8 22.6
0.8 0.4 0.7
0 . 2 % Sodium Sulfamerazine in water 0 . 1 % Sodium Sulfamerazine in water 0 . 5 % Sulfamerazine in mash
21.8 10.6 24.2
22.4 11.1 25.1
0.6 0.6 0.9
0 . 2 % Sodium Sulfamerazine in water 0 . 1 % Sodium Sulfamerazine in water 0 . 5 % Sulfamerazine in mash
18.9 9.5 22.4
19.5 10.0 23.2
0.7 0.5 0.8
0 . 2 % Sodium Sulfamerazine in water 0 . 1 % Sodium Sulfamerazine in water 0 . 5 % Sulfamerazine in mash
0.1 0.0 0.1
0.1 0.0 0.1
0.0 0.0 0.0
Dosage
* The results represent the averages of four poults, t No .treatment 24 hours previous to bleeding.
poults receiving 0.2 percent sodium sulfamerazine in water. The administration of 0.1 percent sodium sulfamerazine in water and 0.25 percent sulfamerazine in mash gave relatively similar blood levels of the free drug. (See Table 2.) The administration of 0.2 percent sodium sulfamethazine to four-week-old turkey poults gave blood levels of free sulfa-
methazine that compared favorably with the levels of sulfamerazine attained in five-week-old turkey poults. From 19.0 to 21.2 mg. of free sulfamethazine were found in 100 ml. of blood. The amount of the free drug in the blood of poults receiving 0.4 percent sulfamethazine in mash was lower, ranging from 13.7 to 14.9 mg. per 100 ml. The use of 0.1 percent sodium
TABLE 2.—Average blood levels of sulfamerazine in eight-week-old turkey poults*
Days
Mgs. per 100 ml. of blood
Mgs. per 100 ml. of blood
Mgs. per 1C0 ml. of blood
Free Drug
Total Drug
Conjugated Drug
0 . 2 % Sodium Sulfamerazine in water 0 . 1 % Sodium Sulfamerazine in water 0 . 5 % Sulfamerazine in mash 0 . 2 5 % Sulfamerazine in mash
13.2 9.3 22.4 9.6
14.2 9.5 23.0 9.7
0.3 0.2 0.6 0.2
0 . 2 % Sodium Sulfamerazine in water 0.17% Sodium Sulfamerazine in water 0 . 5 % Sulfamerazine in mash 0 . 2 5 % Sulfamerazine in mash
18.2 9.9 24.3 8.9
19.1 10.4 25.1 9.4
0.9 0.5 0.8 0.5
0 . 2 % Sodium Sulfamerazine in water 0 . 1 % Sodium Sulfamerazine in water 0 . 5 % Sulfamerazine in mash 0 . 2 5 % Sulfamerazine in mash
17.8 9.7 24.1 7.8
18.4 10.0 24.8 7.9
0.5 0.4 0.7 0.1
Dosage
* The results represent the averages of four poults.
332
STEPHEN GORDETJK, J R . AND MARION LEARNED
TABLE 3.—Average blood levels of sulfamethazine in four-week-old turkey poults*
Days
4
t
Mgs. per 100 ml. of blood
Mgs. per 100 ml. of blood
Mgs. per 100 ml. of blood
Free Drug
Total Drugs
Conjugated Drug
0.2% Sodium Sulfamerazine in water 0.1% Sodium Sulfamerazine in water 0.4% Sulfamethazine in mash
21.2 11.9 14.9
23.9 13.4 16.6
3.2 1.5 1.7
0.2% Sodium Sulfamethazine in water 0.1% Sodium Sulfamethazine in water 0.4% Sulfamethazine in mash
19.0 12.4 14.7
22.2 13.9 16.0
3.2 1.5 1.3
0.2% Sodium Sulfamethazine in water 0.1% Sodium Sulfamethazine in water 0.4% Sulfamethazine in mash
21.2 10.6 13.7
24.4 12.0 15.3
3.2 1.4 1.6
0.2% Sodium Sulfamethazine in water 0.1% Sodium Sulfamethazine in water 0.4% Sulfamethazine in mash
1.1 0.6 0.6
1.2 0.7 0.7
0.1 0.1 0.1
Dosage
* The results represent the averages of four poults, t No treatment 24 hours previous to bleeding. sulfamethazine in drinking water produced blood levels ranging from 10.6 to 12.4 mg. per 100 ml. of blood. Insignificant amounts of sulfamethazine were detected in the blood 24 hours after the discontinuance of treatment. More sulfamethazine appeared in the blood in the conjugated form than
was the case with sulfamerazine. (See Table 3.) Table 4 presents similar data for the poults at the age of nine weeks. The administration of 0.2 percent sodium sulfamethazine in water at this age resulted in blood levels of the free drug that were considerably lower than those
TABLE 4.—Average blood levels of sulfamethazine in nine-week-old turkey poults* Mgs. per 100 ml. of blood
Mgs. per 100 ml. of blood
Mgs. per 1C0 ml. of blood
Free Drug
Total Drug
Conjugated Drug
0.2% Sodium Sulfamethazine in water 0.1% Sodium Sulfamethazine in water 0.4% Sulfamethazine in mash
9.0 8.3 16.6
11.4 10.0 19.4
2.4 1.7 2.8
0.2% Sodium Sulfamethazine in water 0 . 1 % Sodium Sulfamethazine in water 0.4% Sulfamethazine in mash
10.1 8.0 16.6
12.4 10.5 19.4
2.2 2.5 2.7
0.2% Sodium Sulfamethazine in water 0.1% Sodium Sulfamethazine in wtaer 0.4% Sulfamethazine in mash
11.0 7.0 16.7
13.2 8.2 18.5
2.3 1.2 1.8
0.2% Sodium Sulfamethazine in water 0.1% Sodium Sulfamethazine in water 0.4% Sulfamethazine in mash
1.0 0.5 1.1
1.2 0.6 1.5
0.2 0.1 0.3
Days
4t
* The results represent the average of four poults. f No treatment 24 hours previous to sampling.
SULFAMERAZINE AND SULFAMETHAZINE BLOOD LEVELS IN TURKEYS
found at the earlier age. The concentrations of free sulfamethazine at the other levels of treatment (0.1 percent sodium sulfamethazine in water and 0.4 percent sulfamethazine in mash) varied only a little from the previous determinations. Again, only trace amounts of free sulfamethazine were present in the blood of the poults 24 hours after the cessation of treatment. During the course of each study the poults received either medicated drinking water or mash ad libitum. The higher dosages of these sulfonamides given both in the water and in the mash resulted in higher blood concentrations of free drug. Before definite recommendations can be made in regard to proper dosages of these drugs for turkey poults more work should be done in which these sulfonamides are used experimentally as therapeutic agents. Inoculation of four-w'eek-old turkey poults with Eimeria tenella oocysts did not produce any lesions in the ceca or in any other portion of the intestine, demonstrating that this protozoan is not readily introduced into turkeys. No significant pathological changes were observed on post mortem examination of all poults used in the experiment. SUMMARY
1. Average blood concentrations of sulfamerazine in five-week-old turkey poults: 0.2 per cent Sodium sulfamerazine in water— 18.9 to 22.3 mg. per 100 ml. of blood of free drug. 0.1 per cent Sodium sulfamerazine in water—9.4 to 10.6 mg. per 100 ml. of blood of free drug.
333
0.5 per cent Sulfamerazine in mash—21.9 to 24.2 mg. per 100 ml. of blood of free drug.
Average blood concentrations of sulfamerazine in eight-week-old turkey poults: 0.2 per cent Sodium sulfamerazine in water— 13.2 to 18.2 mg. per 100 ml. of blood of free drug. 0.1 per cent Sodium sulfamerazine in water—9.3 to 9.9 mg. per 100 ml. of blood of free drug. 0.5 per cent Sulfamerazine in mash—22.4 to 24.3 mg. per 100 ml. of blood of free drug. 0.25 per cent Sulfamerazine in mash—7.8 to 9.6 mg. Der 100 ml. of blood of free drug.
2. Average blood concentrations of sulfamethazine in four-week-old turkey poults: 0.2 per cent Sodium sulfamethazine in water— 19.0 to 21.2 mg. per 100 ml. of blood of free drug. 0.1 per cent Sodium sulfamethazine in water— 10.6 to 12.4 mg, per 100 ml. of blood of free drug. 0.4 per Cent Sulfamethazine in mash—13.7 to 14.9 mg. per 100 ml. of blood of free drug. Average blood concentrations of sulfamethazine in nine-week-old turkey poults: 0.2 per cent Sodium sulfamethazine in water— 9.0 to 11.0 mg. per 100 ml. of blood of free drug. 0.1 per cent Sodium sulfamethazine in water— 7.0 to 8.3 mg. per 100 ml. of blood of free drug. 0.4 per cent Sulfamethazine in mash—16.6 to 16.7 mg. per 100 ml. of blood of free drug. REFERENCES
Gordeuk, S., Jr., Learned, Marion, and Thorp, W. T. S., Observations on the Chemotherapy of Cecal Coccidiosis, Veterinary Medicine, 42, (1947): 223-228. Thorp, W. T. S., Gordeuk, S. Jr., Glantz, P. J. and Learned, Marion. The Chemotherapy of Cecal Coccidiosis, American Journal of Veterinary Research, 8, (1947): 196-203.