Pharmacokinetics of caffeine in lactating dairy cows.

Because caffeine is metabolized by the hepatic P-450 cytochrome oxidase system, clearance of caffeine is an excellent quantitative test of hepatic function in human beings. It is currently used in much the same way that creatinine clearance is used to assess renal function. Caffeine clearance was measured in lactating dairy cows initially to determine the suitability of caffeine clearance as an indicator of hepatic function in cattle. Pharmacokinetic variables of caffeine were studied in 6 adult lactating dairy cows after i.v. administration of a single dose of caffeine sodium benzoate (2 mg of caffeine/kg of body weight). Caffeine concentration was analyzed by use of an automated enzyme immunoassay. The lower limit of detection of the assay for caffeine in serum was 0.079 micrograms/ml. Serum caffeine concentration-time curves best fit an open two-compartment pharmacokinetic model. Harmonic mean elimination half-life was 3.8 (range, 2.6 to 6.9) hours, and total clearance was 0.118 (range, 0.090 to 0.197) L/kg/h. Milk caffeine concentration was similar to serum concentration 1.5 to 24 hours after caffeine administration. Adverse effects were not observed in cows given caffeine.

Application of an enzyme-multiplied immunoassay technique for determination of caffeine elimination kinetics as a test of liver function in clinically normal dogs.

A commercially available automated enzyme-multiplied immunoassay technique (EMIT) was used to determine serum caffeine concentration after oral and IV administrations of caffeine at dosage of 5 mg/kg of body weight to 12 clinically normal dogs. Dogs were allotted to 2 groups of 6 dogs each; 1 group initially received caffeine orally and the other received caffeine IV. After 72 hours, caffeine administration was repeated in all dogs in the alternate manner. Serum samples were obtained at multiple intervals over 24 hours to determine distribution and elimination kinetics. Analysis of the drug concentration-time data indicated IV elimination half-life (t1/2) of 6.39 +/- 1.87 hours, volume of distribution at steady state of 685.3 +/- 132.2 ml/kg, total body clearance of 1.31 +/- 0.38 ml/min/kg, absorption t1/2 of 1.02 +/- 0.68 hour, oral elimination t1/2 of 6.53 +/- 2.72 hours, lag time after oral administration of 0.0614 +/- 0.0661 hour, highest measured concentration of 5.29 +/- 1.17 micrograms/ml, time to peak concentration of 2.74 +/- 1.30 hours, and bioavailability of 99.4 +/- 19.4%. Data from 6 dogs best fit a 1-compartment open model and those from 6 other dogs best fit a 2-compartment open model. On the basis of data from the 6 dogs that best fit a 2-compartment model, t1/2 of distribution was 0.58 +/- 0.72 hour. Data for oral administration best fit a single absorption phase and a single elimination phase. The increased availability and simplicity of the EMIT offers an opportunity to study the application of caffeine elimination for clinical evaluation of dogs with liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Composition and analysis of cerebrospinal fluid in clinically normal adult cattle.

Cerebrospinal fluid and serum were obtained from 16 clinically normal adult cows (11 dairy, 5 beef). Sodium, potassium, magnesium, total protein, and albumin concentrations, osmolality, and lactate dehydrogenase and creatine kinase activities, were quantified in CSF and serum. Total and differential cell counting, protein electrophoresis, and IgG quantification were performed on CSF. Statistical analyses of these variables, including mean, SEM, range, and 95% confidence intervals, were performed. Effects of blood contamination were evaluated, and were found to be negligible for all measured constituents. Correction factors for CSF creatine kinase and lactate dehydrogenase activities accounting for cellular contamination were developed. Total nucleated cell count was similar to counts in CSF of other species, but higher than values in healthy people. Differential leukocyte count in CSF was similar to that reported in CSF of other domestic animals: mostly lymphocytes, fewer monocytoid cells, and scant neutrophils. Cerebrospinal fluid protein concentration was higher than concentration reported for dogs, goats, and people, but was similar to values reported for horses. Beef cows had higher CSF total protein concentration than did dairy cows; also, beef cows had higher CSF gamma-globulin concentration. The concentration of sodium in CSF was slightly higher than the value in serum, and potassium concentration was lower than the value in serum. In contrast to studies of human beings, CSF osmolality was generally less than serum osmolality in the cows studied. Reference values for CSF electrolyte concentrations and osmolality are useful for diagnosis of salt poisoning and for assessment of the effects of fluid therapy. Magnesium concentration was lower in CSF, compared with serum.(ABSTRACT TRUNCATED AT 250 WORDS)