Pharmacokinetic study of slaframine in lactating goats and transfer into milk

Slaframine is an alkaloidal mycotoxin produced by the fungus Rhizoctonia leguminicola. This mycotoxin is responsible for Blackpatch disease on clover and other legumes and Slobber disease in livestock. Slaframine causes salivation, lacrimation, urination, and defecation in intoxicated animals;The goal of this research was to do a preliminary pharmacokinetic study on slaframine in lactating goats and determine if slaframine was transferred into milk. Slaframine was produced to dose five lactating Saanen goats at a level of 0.05 mg/kg. The slaframine was delivered as an IV bolus dose. Blood, milk, and saliva samples were collected at timed intervals;All samples were analyzed by a newly developed HPLC procedure for slaframine. This procedure used fluorescamine derivatized slaframine to enhance detection 10-fold over previous GC technology. The slaframine derivative was found to be stable for several weeks. The mean recoveries of slaframine from plasma, milk, and saliva were 95%, 91%, and 82%, respectively;The pharmacokinetic study indicated a two compartment model. The half-life for the elimination phase derived for the sample-mean of all five goats was 1.28 hours. The volume of distribution indicated that slaframine was highly protein-bound in goat blood. The mean clearance value of slaframine was 2.6 ml/kg/h, indicating a rapid elimination of slaframine from the body;Due to the unpredictably long half-life of slaframine in the milk, sampling duration was insufficient in all but one goat to study the pharmacokinetics of slaframine in milk. This data would best describe the pharmacokinetic behavior as a two- or three- compartment model. As a two-compartment model, the elimination phase of slaframine in milk was 23 hours. To describe the data as a three-compartment model, (with or without a deep compartment) lower levels of slaframine would need to be detected in plasma. Higher levels of slaframine were seen in milk than in plasma, which correlates well with the pH partition theory. A milk/plasma ratio of 20:1 was obtained using experimental pH values;As a result of slaframine transfer into milk, a potential hazard exists for nursing goats and consumers of goat milk and its by-products. Further studies are necessary for making risk assessments for young animals with the occurrence of slaframine in milk