Effects of lithium carbonate administration to healthy cats.

Lithium carbonate administration to healthy cats was evaluated in 2 controlled studies (a dose-response study and a bone marrow evaluation study) to determine the effectiveness of lithium as a bone marrow stimulant. Lithium carbonate was administrated at dosage ranging from 300 to 1,050 mg/m2 of body surface/d. Complete blood count, serum lithium concentration determination, serum biochemical analysis, urinalysis, and bone marrow aspiration and biopsy were periodically performed. Serum lithium concentration greater than 2 mEq/L was associated with significant decrease in numbers of circulating segmented neutrophils (less than 1,200 cells/microliter; P less than 0.01) and lymphocytes (less than 1,300 cells/microliter; P less than 0.0001), as well as significant (P less than 0.05) decrease in urine specific gravity. Bone marrow evaluation revealed apparent maturation arrest of the neutrophil cell line. Coincident with the changes in laboratory values, the lithium-treated cats became ill. Changes in behavior and vocalization were seen, followed by anorexia, vomiting, and diarrhea. In later stages of intoxication, cats became hyperexcitable and manifested coarse muscular tremors. It was concluded that lithium carbonate does not have potential value as a bone marrow stimulant and is toxic to cats at serum concentration greater than 2 mEq/L.

Esophageal hiatal hernia and megaesophagus complicating tetanus in two dogs.

Two dogs with tetanus developed transient megaesophagus and hiatal hernia associated with gastroesophageal reflux and regurgitation. The megaesophagus and hiatal hernia were diagnosed radiographically and resolved with resolution of the tetanus. These 2 cases, plus previously reported cases, indicate that tetanus can cause megaesophagus and esophageal dysfunction. Therefore, thoracic radiography should be included as part of the diagnostic evaluation of dogs suspected of having tetanus.

Tissue concentrations of clindamycin after multiple oral doses in normal cats.

Eighteen normal cats were randomly allocated into two blocks with three treatment groups and dosed orally with clindamycin aqueous solution for 10 days at a dosage rate of 5.5 mg/kg twice daily (Group 1), 11 mg/kg twice daily (Group 2), or 22 mg/kg once daily (Group 3). At the end of dosing, all cats were killed and tissues were taken for clindamycin concentration analysis. Clindamycin was extracted from tissues using solid-phase extraction columns followed by microbiological assay of clindamycin using a cylinder plate assay using M. luteus. Recovery from each tissue was determined by inoculating known concentrations of clindamycin into drug-naive tissues and comparing the observed concentration from the expected concentration. Confirmation that the bioassay detected clindamycin and not N-desmethylclindamycin, its active metabolite, was done using gas-chromatography-mass-spectrometry. Concentrations were highest in the lung, with tissue:serum ratios greater than 3 in all groups. Concentrations were higher in Group 3 than Group 1 (P less than 0.05). Only liver concentrations in Group 3 were statistically higher than in Group 2, although all tissues except bone marrow and CSF had numerically higher concentrations in Group 3 than Group 2. The tissue:serum ratio was greater than 1 in all tissues studied except bone, cerebrospinal fluid, brain, and skeletal muscle.

Oral clindamycin disposition after single and multiple doses in normal cats.

Eighteen normal cats were randomly allocated into three treatment groups and dosed with clindamycin aqueous solution for 10 days at a dosage rate of: (1) 5.5 mg/kg b.i.d.; (2) 11 mg/kg b.i.d.; or (3) 22 mg/kg once daily. Serum disposition of clindamycin was determined after the first and last dose of clindamycin was given, and was analyzed using model-independent pharmacokinetics by both the trapezoidal rule method and the predictive equation method. Complete blood counts and clinical chemistries were determined before and after the study. The trapezoidal rule method produced similar mean results with much less variance than the predictive equation method. Mean residence time was longer (P less than 0.05) after the high dose (393 +/- 77 min) than after either the low or medium doses (276 +/- 51 and 274 +/- 45 min, respectively). Oral volume of distribution (Vd(ss)/F) after the high dose (3.06 +/- 0.92 l/kg) was larger (P less than 0.05) than that after the low or medium doses (1.62 +/- 0.30 and 1.76 +/- 0.53 l/kg, respectively). Oral Vd(ss)/F was significantly smaller (P less than 0.001) after the last dose than after the first dose when analyzed by treatment group. Significant (P less than 0.01) decreases in the leukogram and erythrogram were observed, due to the large amount of blood collected for drug analysis. No clinical signs of drug intoxication were observed, and no drug-related necropsy findings were found.