Pharmacokinetics of lithium in pigs

Lithium was administered to young pigs in order to estimate its pharmacokinetic parameters in this species and a suitable dosage for chronic psychopharmacological experiments. Distribution time (10 h) and volume (1 l/kg), elimination half-life (10–20 h), toxic plasma levels (about 1.4 mEq/l) are closely similar to those reported in man. A chronic oral administration of 0.5 mEq/kg twice a day provides minimal plasma levels of 0.5 to 1.0 mEq/l, without toxic side effects.     

Pharmacokinetics of lithium in sheep

Lithium was administered to adult sheep to estimate its pharmacokinetic parameters and a suitable dosage for chronic psychopharmacological experiments. The triexponential decline of plasma lithium levels was tentatively interpreted with a three-compartment, open-model of distribution. Sheep differed from other species by the following features: high faecal excretion of lithium, recycling of lithium through the salivary secretion and low absorption rate of the orally-administered drug. A chronic oral administration of 1 mmol/kg once daily provided minimal plasma levels of about 1 mmol/l, without toxic side-effects. The results are discussed with respect to comparative pharmacokinetics of lithium and its potential use in the treatment of behavioral disorders of farm animals.     

Pharmacokinetics of lithium in the dog

The pharmacokinetics of lithium were determined in eight adult dogs. The data were fitted to a two-compartment model. Single intravenous doses of lithium chloride, and single oral doses of lithium carbonate were used. The mean plasma lithium half-life (t1/2) following the single intravenous dose was 21.6 h, and the mean apparent specific volume of distribution of the central compartment (V'c) was 0.189 l/kg. Mean bioavailability was 78.8% following oral administration.     

Effect of background serum lithium concentrations on the accuracy of lithium dilution cardiac output determination in dogs

OBJECTIVES: To assess the effect of increasing serum lithium concentrations on lithium dilution cardiac output (LiDCO) determination and to determine the ability to predict the serum lithium concentration from the cumulative lithium chloride dosage. ANIMALS: 10 dogs (7 males, 3 females). PROCEDURE: Cardiac output (CO) was determined in anesthetized dogs by measuring LiDCO and thermodilution cardiac output (TDCO). The effect of the serum lithium concentration on LiDCO was assessed by observing the agreement between TDCO and LiDCO at various serum lithium concentrations. Also, cumulative lithium chloride dosage was compared with the corresponding serum lithium concentrations. RESULTS: 44 paired observations were used. The linear regression analysis for the effect of the serum lithium concentration on the agreement between TDCO and LiDCO revealed a slope of -1.530 (95% confidence interval [CI], -2.388 to -0.671) and a y-intercept of 0.011 (r2 = 0.235). The linear regression analysis for the effect of the cumulative lithium chloride dosage on the serum lithium concentration revealed a slope of 2.291 (95% CI, 2.153 to 2.429) and a y-intercept of 0.008 (r2 = 0.969). CONCLUSIONS AND CLINICAL RELEVANCE: The LiDCO measurement increased slightly as the serum lithium concentration increased. This error was not clinically relevant and was minimal at a serum lithium concentration of 0.1 mmol/L and modest at a concentration of 0.4 mmol/L. The serum lithium concentration can be reliably predicted from the cumulative lithium dosage if lithium chloride is administered often within a short period.     

Effects of lithium on aggressive behaviour in domestic pigs

Lithium carbonate (0.75 and 1 mEq/kg daily) mixed with food was chronically administered to growing pigs. Control animals received equivalent amounts of sodium carbonate. Added lithium decreased intra-group aggression occurring when access to food was restricted but did not prevent aggression and fighting observed after mixing pigs from different origins. The results are discussed in relation to the current interpretations of the psychopharmacological activity of lithium, and the prospective value of using lithium in pig intensive husbandry for controlling behavioural disorders is examined.     

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.     

锂对光合细菌生长和罗非鱼免疫功能的影响

为锂元素在水产免疫中的应用作了探讨。主要包括无机锂对光合细菌和罗非鱼的毒性,无机锂对光合细菌的生长和罗非鱼免疫因子的影响,含锂培养的光合细菌体外抑菌和体内对罗非鱼免疫因子的影响等。试验结果表明,锂对光合细菌最小抑菌浓度为50mg/kg,最小杀菌浓度为100mg/kg,在8mg/kg～12mg/kg间对光合细菌生长具有显著促进作用。锂对罗非鱼半致死浓度为0.5mg/kg,安全浓度为0.1mg/kg,无机锂可以提高罗非鱼血清(浆)中溶菌和抗菌活力、增加免疫细胞的核质比,但吞噬细胞活力和免疫细胞数量没有增加;含锂培养的光合细菌细胞破碎物体外具有显著抑制弧菌的能力,体内可以显著提高罗非鱼血清中溶菌活力。说明锂作为免疫激活剂,在水产上应用是可行的,同时可以用光合细菌作为锂的载体来消除无机锂对罗非鱼的毒性。     

Cardiac output determination by use of lithium dilution during exercise in horses

OBJECTIVE: To compare cardiac output (CO) obtained by the lithium dilution method (LiDCO) with CO calculated from the Fick principle (FickCO), in horses maximally exercising on a high-speed treadmill. ANIMALS: 13 Thoroughbreds. PROCEDURES: In part 1 of the study, 5 horses performed a warm-up (walk, trot, and canter) and exercise test (walk, trot, canter, and gallop [90% to 100% maximum oxygen consumption [{[Formula: see text]O(2)max}]) with measurements of LiDCO and FickCO obtained simultaneously after 60 seconds at each exercise level, for a total of 7 measurements. In part 2 of the study, 8 horses performed a warm-up (walk, trot, and canter) followed by an exercise test (walk and gallop [90% to 100% [Formula: see text]O(2)max], repeated twice). Measurements of LiDCO and FickCO were obtained 60 seconds into the first walk and each gallop of the exercise tests, for a total of 3 measurements. RESULTS: Cardiac output increased significantly with increasing speeds by use of both methods. In part 1, lithium dilution significantly overestimated CO, compared with the Fick principle, during the exercise test (as both injection number and exercise intensity increased). Mean +/- SD bias was 246 +/- 264 mL of blood/min/kg in part 1 and 67 +/- 100mL of blood/kg/min in part 2. Three injections of lithium (part 2) did not result in the same degree of overestimation of LiDCO that was observed with 7 injections (part 1). CONCLUSIONS AND CLINICAL RELEVANCE: Lithium dilution may be an acceptable substitute for the Fick principle as a means to measure CO in maximally exercising client-owned horses.     

Pharmacokinetics and toxic effects of lithium chloride after intravenous adminstration in conscious horses

OBJECTIVE: To determine the pharmacokinetics and toxic effects associated with IV administration of lithium chloride (LiCl) to conscious healthy horses. ANIMALS: 6 healthy Standardbred horses. PROCEDURE: Twenty 3-mmol boluses of LiCl (0.15 mmol/L) were injected IV at 3-minute intervals (total dose, 60 mmol) during a 1-hour period. Blood samples for measurement of serum lithium concentrations were collected before injection and up to 24 hours after injection. Behavioral and systemic toxic effects of LiCl were also assessed. RESULTS: Lithium elimination could best be described by a 3-compartment model for 5 of the 6 horses. Mean peak serum concentration was 0.561 mmol/L (range, 0.529 to 0.613 mmol/L), with actual measured mean serum value of 0.575 mmol/L (range, 0.52 to 0.67 mmol/L) at 2.5 minutes after administration of the last bolus. Half-life was 43.5 hours (range, 32 to 84 hours), and after 24 hours, mean serum lithium concentration was 0.13+/-0.05 mmol/L (range, 0.07 to 0.21 mmol/L). The 60-mmol dose of LiCl did not produce significant differences in any measured hematologic or biochemical variables, gastrointestinal motility, or ECG variables evaluated during the study period. CONCLUSIONS AND CLINICAL RELEVANCE: Distribution of lithium best fit a 3-compartment model, and clearance of the electrolyte was slow. Healthy horses remained unaffected by LiCl at doses that exceeded those required for determination of cardiac output. Peak serum concentrations were less than steady-state serum concentrations that reportedly cause toxic effects in other species.     

Comparison of lithium dilution and thermodilution cardiac output measurements in anaesthetised neonatal foals

Knowledge of cardiac output is expected to help guide the treatment of hypotension associated with critical illness and/or anaesthesia in neonatal foals. However, a practical and safe method of measuring cardiac output has not been described for the foal. Lithum dilution, a new method of cardiac output determination not requiring cardiac catheterisation, has recently been reported in mature horses. We compared this method to thermodilution in isoflurane-anaesthetised foals age 30-42 h and found good agreement between the 2 methods in a range of cardiac outputs 5.4-20.4 l/min. The lithium dilution technique is a practical and reliable method of measuring cardiac output in anaesthetised neonatal foals, and warrants investigation in critically ill conscious foals.     

Use of lithium for treatment of estrogen-induced bone marrow hypoplasia in a dog.

Marrow hypoplasia and consequent pancytopenia caused by simultaneous administration of estradiol cyclopentylpropionate and diethylstilbestrol were diagnosed in a 6-year-old Old English Sheep-dog. The dog was treated with lithium carbonate (11 mg/kg of body weight, PO, q 12 h) for 6 weeks. Despite the generally grave prognosis associated with estrogen toxicosis, lithium treatment was apparently successful in inducing regeneration of the bone marrow. Side effects of lithium treatment were not noticed.     

The effect of lithium chloride on renal structure and sodium-potassium-adenosine triphosphatase activity in dogs

Lithium chloride was given intraperitoneally to dogs at a dosage of 125 mg/kg body weight for three days. Kidneys were removed for morphologic examination and quantitation of sodium-potassium-adenosine triphosphatase (Na-K-ATPase) activities in cortical and medullary tissue. Light microscopy showed no changes in the kidneys, but cytoplasmic vacuolation and dilatation of the cisternae of the endoplasmic reticulum were seen ultrastructurally in the epithelial cells of the distal tubule and cortical and medullary collecting ducts. Mean cortical Na-K-ATPase activity was 1.49 +/- 0.25 and 1.70 +/- 0.31 mumoles inorganic phosphate/mg protein/hour in control and experimental groups respectively. Mean medullary Na-K-ATPase activity was 4.71 +/- 0.41 and 5.01 +/- 0.47 mumoles inorganic phosphate/mg protein/hour in control and experimental groups respectively. It was concluded that lithium produced morphologic changes in the distal nephron, but had no effect on renal Na-K-ATPase activity.     

The use of lithium carbonate to prevent lomustine-induced myelosuppression in dogs: a pilot study

This was a preliminary investigation of the use of lithium to prevent lomustine-induced myelosuppression. Four 10 to 11 kg beagles received lomustine 20 to 30 mg, PO, q3wk, with cephalexin prophylaxis. Two dogs also received lithium, 150 to 300 mg, PO, q12h. Lithium blood concentrations fluctuated in and out of therapeutic interval. Lithium was discontinued in one dog in week 13, and in the other dog in week 38, due to toxicoses. All dogs developed grade 1 to 4 neutropenia after each lomustine treatment. In dogs receiving lomustine only, platelet concentrations decreased from 274 and 293 × 10(9)/L in week 1, to 178 and 218 × 10(9)/L in weeks 38 and 13, respectively. In dogs receiving lomustine and lithium, platelet concentrations decreased from 351 and 288 × 10(9)/L in week 1, to 214 and 212 × 10(9)/L, in weeks 36 and 13, respectively. Lithium did not prevent lomustine-induced myelosuppression and had important side-effects.     

Assessment of lithium dilution cardiac output as a technique for measurement of cardiac output in dogs

OBJECTIVES: To determine agreement of cardiac output measured by use of lithium dilution cardiac output (LiDCO) and thermodilution cardiac output (TDCO) techniques in dogs and to determine agreement of low- and high-dose LiDCO with TDCO. ANIMALS: 10 dogs (7 males, 3 females). PROCEDURE: Cardiac output was measured in anesthetized dogs by use of LiDCO and TDCO techniques. Four rates of cardiac output were induced by occlusion of the caudal vena cava, changes in depth of anesthesia, or administration of dobutamine. Lithium dilution cardiac output was performed, using 2 doses of lithium chloride (low and high dose). Each rate of cardiac output allowed 4 comparisons between LiDCO and TDCO. RESULTS: 160 comparisons were determined of which 68 were excluded. The remaining 92 comparisons had values ranging from 1.10 to 12.80 L/min. Intraclass correlation coefficient (ICC) between low-dose LiDCO and TDCO was 0.9898 and between high-dose LiDCO and TDCO was 0.9896. When all LiDCO determinations were pooled, ICC was 0.9894. For determinations of cardiac output < 5.0 L/min, ICC was 0.9730. Mean +/- SD of the differences of TDCO minus LiDCO for all measurements was -0.084+/-0.465 L/min, and mean of TDCO minus LiDCO for cardiac outputs < 5.0 L/min was -0.002+/-0.245 L/min. CONCLUSIONS AND CLINICAL RELEVANCE: The LiDCO technique is a suitable substitute for TDCO to measure cardiac output in dogs. Use of LiDCO eliminates the need for catheterization of a pulmonary artery and could increase use of cardiac output monitoring, which may improve management of cardiovascularly unstable animals.     

Evaluation of hemodynamic measurements, including lithium dilution cardiac output, in anesthetized dogs undergoing ovariohysterectomy

OBJECTIVE: To measure cardiac output in healthy female anesthetized dogs by use of lithium dilution cardiac output and determine whether changes in mean arterial pressure were caused by changes in cardiac output or systemic vascular resistance. DESIGN: Prospective clinical study. ANIMALS: 20 healthy female dogs. PROCEDURE: Dogs were anesthetized for ovariohysterectomy. Ten dogs breathed spontaneously throughout anesthesia, and 10 dogs received intermittent positive-pressure ventilation. Cardiovascular and respiratory measurements, including lithium dilution cardiac output, were performed during anesthesia and surgery. RESULTS: Mean arterial pressure and systemic vascular resistance index were low after induction of anesthesia and just prior to surgery and increased significantly after surgery began. Cardiac index (cardiac output indexed to body surface area) did not change significantly throughout anesthesia and surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Results provide baseline data for cardiac output and cardiac index measurements during clinical anesthesia and surgery in dogs. Changes in mean arterial pressure do not necessarily reflect corresponding changes in cardiac index.