Effects of piroxicam on tissue distribution of sulfadimidine in West African Dwarf male and female goats

Abstract

Cases of Stevens-Johnson syndrome have been increasingly reported in Nigeria by individuals who consumed meat products of animals especially goats injected sulfonamides. Hence, tissue distribution and residues of intramuscular sulfadimidine were studied in West African Dwarf (WAD) goats. Twenty goats divided into two groups of 10 each (five males; five females) weighing 10.4 ± 1.63 kg were administered intramuscular sulfadimidine (100 mg/kg body weight), and the second group was coadministered 5 mg/kg of piroxicam via right and left thigh muscle, respectively. Samples of the liver, kidney, spleen, heart, lung, intestine, brain, and skeletal muscle were collected into sterile cellophane bags. Two untreated goats were killed and used for preparation of tissue standards. The tissue samples were stored frozen for analysis. High concentration of sulfadimidine residues was found in all the tissues of goats administered sulfadimidine as well as tissues of goats coadministered sulfadimidine/piroxicam for up to 30 days postdrug administration. Generally, residues of sulfadimidine were observed to be significantly higher than the acceptable limit (0.1 ppm). Hence, consumption of meats from WAD goats administered sulfadimidine may pose very high risk of Stevens-Johnson syndrome in sensitive humans. As such consumption of such meats should be avoided.

Unique Pharmacokinetic and Pharmacodynamic Parameters of Antimicrobials in Goats

“…The presence of sulfadimidine residues (>0.1 ppm) in the liver, kidney, skeletal muscle, spleen, lung, brain and heart after administration of the drug (100 mg/kg) shows that the withdrawal period is longer than 30 days. Hence, sulfadimidine is not easily excreted in West African dwarf goats [13]. This may be due to the presence of desamino-sulfonamide, a sulfadimidine metabolite [75] which is eliminated slowly, thereby increasing the withdrawal time [76].…”

“…This may be due to the presence of desamino-sulfonamide, a sulfadimidine metabolite [75] which is eliminated slowly, thereby increasing the withdrawal time [76]. Lack of adequate water to dilute crystals of sulfadimidine in the kidney can lead to crystalluria that can consequently cause nephrosis in the affected animals [44], and consumptions of meats with high residues of sulfadimidine can cause Steven-Johnson syndrome in sensitive humans who may be slow or fast acetylators [13,23]. Based on the tissue tolerance limit in cattle (5 ppm), the withdrawal period for tulathromycin is 19 days in cattle and 34 days in goat when administered subcutaneously [5].…”

“…There are up to 800 million goats in the world [3]. The economic species of goats spread across the globe are not limited to Teddy, Kilis, Ardi, West African Dwarf, Black Bengal, Indian native, Murciano-Granadina, Angora, Red Sokoto, Boer and Nubian goats [4][5][6][7][8][9][10][11][12][13]. However, the diseases of goats include colibacillosis, salmonellosis, staphylococcosis and streptococcosis, among others [14].…”

“…However, the diseases of goats include colibacillosis, salmonellosis, staphylococcosis and streptococcosis, among others [14]. Age, sex, dosage formulation, route of administration and dose of antimicrobials affect pharmacokinetics and pharmacodynamics of antimicrobials in goats [13]. For example, female West African dwarf goats are more sensitive to sulfadimidine than male West African dwarf goats [15].…”

“…However, Capra aegagrus hircus is the most popular domesticated from their wild progenitor, bezoar (Capra aegagrus) [21,22]. Also, antimicrobials such as sulfonamides, trimethoprimsulfamethoxazole, aminopenicillins, cephalosporins and quinolones could cause Stevens-Johnson syndrome in humans that eat goat meat which has the drugs residues [23] and tissue residues above threshold (2 ppm) could be found in the skeletal muscle, liver, kidney, milk, brain, intestine, heart and lung of goats which could portend threat to public health [13]. Although goats are domesticated 10,500 years ago, the genomic regions differentiating domestic goats from wild goats are associated to genes of the nervous system, immunity and productivity traits; 20 are common to Capra and Ovis [24] indicating the possible relevance of pharmacogenomics which is the study of how genes affect animal response to drugs.…”