Single-injection method for evaluation of renal function with 14C-inulin and 3H-tetraethylammonium bromide in dogs and cats

A double-isotope single-injection method without urine collection for the estimation of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in dogs and cats was evaluated. The GFR was determined, using 14C-inulin and ERPF was determined, using [3H]tetraethylammonium bromide. Using a modified single exponential, 1-compartment mathematical model, the renal clearance of these solutes was estimated with a plasma radioactivity disappearance curve constructed from samples collected over a 150-minute time period. In 25 dogs, GFR, ERPF, and filtration fraction were 3.55 +/- 0.14 ml/kg/min, 10.51 +/- 0.72 ml/kg/min, and 0.34 +/- 0.02, respectively. In 25 cats, GFR, ERPF, and filtration fraction were 3.24 +/- 0.14 ml/kg/min, 8.14 +/- 0.53 ml/kg/min, and 0.39 +/- 0.02, respectively. This time-efficient and reliable method, using beta-emitting isotopes, yielded renal functional values well within the normal ranges reported by a variety of other isotopic and nonisotopic procedures. The advantages of the present procedure over previous double-isotope single-injection methods include the use of less costly, lower energy-using, and less penetrating beta emittors, as well as a shortened blood sampling schedule.     

Hepatobiliary transport of indocyanine green and sulfobromophthalein in fed and fasted horses

Fasting is associated with unconjugated hyperbilirubinemia in several species, including the horse. Studies in ponies showed that a 3-day fast decreased plasma clearance of bilirubin, cholic acid, and sulfobromophthalein (BSP). Since these organic anions are conjugated with different substrates, it is possible that observed differences in plasma clearance result from a general decrease in hepatic conjugating capacity during the animals' fasting. To test this hypothesis, the effects of a 3-day fast on plasma clearance of IV injected BSP (4.4 to 5.1 mg/kg), which is conjugated to glutathione, and indocyanine green (ICG; 0.8 to 1.1 mg/kg), which is not conjugated, were studied in 10 healthy horses and 2 ponies with diverted enterohepatic circulations (indwelling T tubes). Blood samples were obtained for 30 minutes after injection, and bile samples from ponies were obtained for 3 hours. Fasting increased plasma bilirubin concentration in all animals studied (from 1.03 +/- 0.337 mg/dl in control animals to 3.49 +/- 1.01 mg/dl in fasted animals). Kinetic values of ICG disappearance were determined from single exponential functions, and those for BSP were determined from both single and curvilinear (2-exponential) functions. Plasma clearance of BSP in fed horses (8.65 +/- 1.02 ml X min-1 X kg-1) was greater than clearance of ICG (3.54 +/- 0.67 ml X min-1 X kg-1), results similar to those reported in dogs, cats, rats, and persons. Fasting significantly decreased fractional plasma disappearance rate of both BSP (-36%) and ICG (-58%) and similarly reduced plasma clearance (BSP,-48%; ICG,-55%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Estimation of Glomerular Filtration Rate in Normal Sheep by the Disappearance of Iohexol from Serum

Nesje, M., Flåøsyen, A. and Moe, L., 1997. Estimation of glomerular filtration rate in normal sheep by the disappearance of iohexol from serum. Veterinary Research Communications, 21 (1), 29-35. The aim of the study was to establish reference values for glomerular filtration rate (GFR) in healthy sheep from the clearance of iohexol in serum. Fifteen healthy sheep were tested twice with 14 to 21 days between tests. No side-effects were observed after iohexol injections and all the sheep were clinically normal during and after the study. The mean clearance of iohexol estimated by the two-compartment method was 1.8 ml/min per kg (95% CI = 1.6-2.0) in the first trial and 1.7 ml/min per kg (1.5-1.9) in the second trial. The mean GFRiohexol estimated by a one-compartment method was 1.9 ml/min per kg (1.7-2.2) in the first trial and 1.8 ml/min per kg (1.6-2.0) in the second. The GFR values were similar to those reported for the inulin method. The results indicate that the iohexol method is valid for estimating GFR in sheep, and it is easier to perform than the inulin method.     

Pharmacokinetics of flunixin meglumine in donkeys, mules, and horses

OBJECTIVE: To compare serum disposition of flunixin meglumine after i.v. administration of a bolus to horses, donkeys, and mules. ANIMALS: 3 clinically normal horses, 5 clinically normal donkeys, and 5 clinically normal mules. PROCEDURE: Blood samples were collected at time zero (before) and 5, 10, 15, 30, and 45 minutes, and at 1, 1.25, 1.5, 1.75, 2, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, and 8 hours after i.v. administration of a bolus of flunixin meglumine (1.1 mg/kg of body weight). Serum was analyzed in duplicate by the use of high-performance liquid chromatography for determination of flunixin meglumine concentrations. The serum concentration-time curve for each horse, donkey, and mule were analyzed separately to estimate noncompartmental pharmacokinetic variables RESULTS: Mean (+/-SD) area under the curve for donkeys (646 +/- 148 minute x microg/ml) was significantly less than for horses (976 +/- 168 minute x microg/ml) or for mules (860 +/- 343 minute x microg/ml). Mean residence time for donkeys (54.6 +/- 7 minutes) was significantly less than for horses (110 +/- 24 minutes) or for mules (93 +/- 30 minutes). Mean total body clearance for donkeys (1.78 +/- 0.5 ml/kg/h) was significantly different from that for horses (1.14 +/- 0.18 ml/kg/h) but not from that for mules (1.4 +/- 0.5 ml/kg/h). Significant differences were not found between horses and mules for any pharmacokinetic variable. CONCLUSION AND CLINICAL RELEVANCE: Significant differences exist with regard to serum disposition of flunixin meglumine in donkeys, compared with that for horses and mules. Consequently, flunixin meglumine dosing regimens used in horses may be inappropriate for use in donkeys.     

Clearance of indocyanine green in dogs with partial hepatectomy, hepatic duct ligation, and passive hepatic congestion

Clearance of 5 submaximal doses of indocyanine green (ICG) was measured in 5 dogs to determine the maximal removal rate (0.188 mg/kg of body weight/min) and Michaelis constant (Km, 1.25 mg/kg). From these results, 5 mg of ICG/kg of body weight was chosen on the basis of the recommendation that the dose should be at least 4 X Km to achieve sensitivity as a measure of hepatic function and independence from hepatic blood flow. Clearances of low (0.5 mg/kg) and high (5 mg/kg) doses of ICG were measured in 35 healthy dogs to determine reference values. Fractional disappearance was 15.1 +/- 10%/min for the low dose and 3.9 +/- 1%/min for the high dose; plasma half-life was 6.3 +/- 3.6 minutes and 19 +/- 4.8 minutes, respectively. The sensitivity of 2 doses of ICG was evaluated in dogs with 20% and 40% hepatectomy, nonhyperbilirubinemic obstructive cholestasis, or hepatic congestion; sham-operated dogs served as controls. Fractional disappearance and plasma half-life of ICG in the 40% hepatectomy and hepatic congestion groups were significantly different (P less than 0.05) from those in controls using both ICG doses, indicating that both doses were affected by hepatic perfusion, as well as hepatic mass. The fractional disappearance of the dye in the cholestasis group also differed significantly (P less than 0.05) from that of the controls at the high dose. Plasma clearance of both doses by dogs with 20% hepatectomy was not significantly different from that of controls.     

Clinical evaluation of glomerular function: 24-hour creatinine clearance in dogs.

Methods of renal clearance to measure glomerular filtration rate (GFR) were compared with plasma creatinine concentration in clinically normal and partially nephrectomized dogs. Glomerular filtration rate was measured by use of a simple 24-hour creatinine clearance method in 36 normal female Beagles. Mean values were 57.6 +/- 9.3 ml/minute/m2 of body surface or 3.7 +/- 0.77 ml/minute/kg of body weight. Variability of this measurement was considerable, as determined in 4 dogs studied on 4 consecutive days. Glomerular filtration rate was measured in the same 36 dogs while they were under anesthesia, using short clearance periods to compare inulin and endogenous creatinine clearance. Mean values for inulin were 41.8 +/- 13.9 ml/minute/m2 of body surface. A close agreement with creatinine clearance was found (correlation coefficient, 0.998). Mean plasma creatinine concentration was 0.82 (range, 0.5--1.0) mg/100 ml. The value of GFR measurement compared with plasma creatinine concentration was determined in 10 dogs after 75% nephrectomy. Sixty days after partial nephrectomy, GFR was reduced to 61% of normal. Mean plasma creatinine and blood urea nitrogen were 1.2 +/- 0.14 mg/100 ml and 20.4 +/- 7.1 mg/100 ml, respectively. Thus, the detection of reduced renal function may be uncertain when plasma creatinine or blood urea nitrogen are used as a means of evaluating renal function. It was concluded that a simple method of creatinine clearance is a sensitive and useful measurement to detect early or borderline reduction in glomerular function.     

A comparative study of the pharmacokinetics of thiopental in the rabbit, sheep and dog

The central arterial pharmacokinetics of thiopental were studied in six rabbits, six sheep and six dogs after a short infusion at approximately 10 mg/kg min. Thiopental was infused to a defined electro-encephalographic endpoint (EEG burst suppression). The time to reach early burst suppression was longer in the dog (3.9 +/- 0.5 min) compared with the sheep (3.0 +/- 0.6 min) and the rabbit (2.5 +/- 0.5 min). The total dose required to produce the same level of EEG activity was higher in the dog (35.9 +/- 6.8 mg/kg) compared with the sheep (24.3 +/- 5.3 mg/kg) and the rabbit (21.6 +/- 6.8 mg/kg). The plasma concentration-time data for each animal was fitted using non-linear regression to a bi- or tri-exponential function. In all animals, the plasma-time profile was best described as a tri-exponential decay. The initial volume of distribution was similar in all three species (rabbit, 38.6 +/- 10.0 mg/kg; sheep, 44.5 +/- 9.1 ml/kg; dog, 38.1 +/- 18.4 ml/kg). The maximum arterial plasma thiopental concentration achieved at EEG burst suppression was higher in the sheep (221.8 +/- 27.9 micrograms/ml) than the dog (164.7 +/- 29.9 micrograms/ml) or the rabbit (112.3 +/- 15.1 micrograms/ml). Thiopental distribution clearance was slower in the sheep (43.6 +/- 15.1 ml/min/kg) compared with the rabbit (110.5 +/- 18.7 ml/min kg) and the dog (97.2 +/- 47.2 ml/min kg). Elimination half-life was extended in the sheep (251.9 +/- 107.8 min) and dog (182.4 +/- 57.9 min) relative to the rabbit (43.1 +/- 3.4 min).(ABSTRACT TRUNCATED AT 250 WORDS)     

USE OF 99mTc-MERCAPTOACETYLTRIGLYCINE TO EVALUATE RENAL FUNCTION IN HORSES

Ten healthy horses were injected intravenously with 99mTc-MAG3 and the disappearance of radioactivity from the blood was measured. The total body clearance (Cl(B)) and elimination half-life (t1/2(beta)) were 7.9 +/- 1.5 ml/kg/minute and 32.8 +/- 4.1 minutes, respectively. The disappearance of 99mTc-MAG3 from the blood of 2 horses with compromised renal function was also measured. The data suggest that 99mTc-MAG3 is a useful and clinically applicable radiopharmaceutical for measurement of effective renal blood flow in the horse.     

Determination of excretion of inulin, creatinine, sodium sulfanilate, and phenolsulfonphthalein to assess renal function in goats

Excretion of creatinine, sodium sulfanilate (SS), and phenolsulfonphthalein (PSP) was studied in healthy goats. In conscious goats, mean (+/- SEM) inulin clearance was 2.26 +/- 0.08 ml/min/kg of body weight. Endogenous creatinine clearance, 1.97 +/- 0.09 ml/min/kg, underestimated inulin clearance (P less than 0.01), probably because of the presence of noncreatinine chromogens in caprine plasma. The estimated renal clearance of PSP was 6.88 +/- 0.39 ml/min/kg, whereas the estimated renal clearance of SS was 3.71 +/- 0.39 ml/min/kg. Both exceeded inulin clearance (P less than 0.01), confirming renal tubular secretion of both compounds. In 6 anesthetized goats, exogenous creatinine clearance and SS clearance exceeded inulin clearance (P less than 0.05). Results of stop-flow experiments documented secretion of creatinine and SS by the proximal portion of the caprine nephron. Plasma half-life of PSP in uninephrectomized goats exceeded that in intact goats (20.2 +/- 1.5 min vs 11.9 +/- 0.7 min; P less than 0.01). Similarly, plasma half-life of SS was greater in goats after uninephrectomy (58.2 +/- 6.2 min vs 30.4 +/- 1.2 min; P less than 0.01).     

Comparative study of the pharmacokinetics of alfentanil in rabbits, sheep, and dogs

The central arterial pharmacokinetics of alfentanil, a short-acting opioid agonist, were studied in rabbits, sheep, and dogs after short-duration infusion of the drug. Alfentanil was infused until a set end point (high-amplitude, slow-wave activity on the EEG) was reached. This required a larger alfentanil dose and a higher alfentanil arterial concentration in sheep, compared with rabbits and dogs. The plasma concentration-time data for each animal were fitted, using nonlinear regression, and in all animals, were best described by use of a triexponential function. In this study, differences in the disposition kinetics of alfentanil among the 3 species were found for only distribution clearance and initial distribution half-life. In dogs, compared with rabbits and sheep, the first distribution half-life was longer, probably because of pronounced drug-induced bradycardia (mean +/- SD, 48 +/- 21 beats/min). Distribution clearance was faster in sheep, compared with dogs, also probably because of better blood flow in sheep. Elimination half-life was similar in all species (rabbits, 62.4 +/- 11.3 minutes; sheep, 65.1 +/- 27.1 minutes; dogs, 58.3 +/- 10.3 minutes). This rapid half-life resulted from a small steady-state volume of distribution (rabbits, 908.3 +/- 269.0 ml/kg; sheep, 720.0 +/- 306.7 ml/kg; dogs, 597.7 +/- 290.2 ml/kg) and rapid systemic clearance (rabbits, 19.4 +/- 5.3 ml/min/kg; sheep, 13.3 +/- 3.0 ml/min/kg; dogs, 18.7 +/- 7.5 ml/min/kg). On the basis of these pharmacokinetic variables, alfentanil should have short duration of action in rabbits, sheep, and dogs. This may be beneficial in veterinary practice where rapid recovery would be expected after bolus administration for short procedures or after infusion for longer procedures.     

Single-injection method for evaluation of renal function with 3H-inulin and 14C-tetraethylammonium bromide in conscious unrestrained Sprague-Dawley rats

A single-injection, double-isotope method for simultaneously determining glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in conscious, unrestrained rats was evaluated. 3H-inulin and 14C-tetraethylammonium bromide were used to determine GFR and ERPF, respectively. Using a modified, single exponential, 1-compartment, mathematical model, solute clearance was estimated, using a plasma radioactivity disappearance curve constructed from samples collected during a 60-minute period. In 12 healthy, conscious, adult male Sprague-Dawley rats, the mean (+/- SEM) GFR, ERPF, and filtration fraction were 5.65 +/- 0.40 ml/min/kg, 13.92 +/- 0.82 ml/min/kg, and 0.41 +/- 0.03, respectively. In 7 adult male Sprague-Dawley rats that had undergone a three-quarter nephrectomy 6 weeks prior to study, the mean GFR, ERPF, and filtration fraction were 2.69 +/- 0.36 ml/min/kg, 7.02 +/- 0.90 ml/min/kg, and 0.39 +/- 0.03, respectively. In 37 adult male rats in various stages of renal disease, the mean GFR and ERPF correlated significantly (r = 0.85, P less than 0.001 and r = 0.83, P less than 0.001, respectively) with the reciprocal of plasma creatinine. The single-injection, double-isotope technique yielded functional values similar to those reported for healthy rats in which other clearance methods were used. Using this technique, we were able to detect alterations associated with various degrees of renal functional loss. The technique enabled us to evaluate conscious, unrestrained rats, eliminated the need to collect urine, and required short blood collection times (60 min) and small volumes (0.1 ml) of plasma.     

Comparative benzylpenicillin pharmacokinetics in the dromedary Camelus dromedarius and in sheep

Benzylpenicillin pharmacokinetics were compared in the dromedary Camelus dromedarius (n = 5) and in sheep (n = 5) after administration of a single intravenous injection of benzylpenicillin. The data were described by an open three-compartment model with elimination from the central compartment. Body clearance (Clb) was 4.87 +/- 0.63 ml/min/kg in the dromedary and 9.17 +/- 1.39 ml/min/kg in sheep, the steady-state volumes of distribution (Vss) were 0.151 +/- 0.023 l/kg and 0.165 +/- 0.038 l/kg and the mean residence times (MRT) 27.34 +/- 1.38 min and 14.95 +/- 4.16 min in the dromedary and in sheep, respectively. It was concluded that benzylpenicillin elimination occurs more slowly in the dromedary than in sheep and that use of the same dosage regimen for the two ruminant species may lead to significant differences in plasma concentrations and therapeutic efficacy.     

围产期绵羊血浆胰岛素样生长因子-1水平的动态变化及胆酸负荷对其的影响

:6只成年考力代妊娠母羊 ,经 2周适应饲养后随机分为两组。在安装颈静脉血管瘘后 ,一组通过颈静脉瘘管灌注胆酸 ( 2mg/kg) ,另一组同步灌注等量的生理盐水。间隔 1 4天灌注 1次 ,直至分娩。在灌注前和灌注后每天定时采取血样 ,测定血浆IGF -1水平 ,研究绵羊围产期血浆IGF -1的动态变化及胆酸负荷对其的影响。结果表明 ,围产期母羊血浆IGF -1正常水平在 572 .1 0± 2 0 7.1 5ng/ml～ 787.1 2±4 2 .33ng/ml之间 ,没有明显的动态变化规律。但分娩后的IGF -1平均水平显著低于分娩前平均值 ,分别是 639.54± 56.37ng/ml和 70 5.2 1± 52 .2 4ng/ml(P <0 .0 5)。胆酸灌注组母羊妊娠后期血浆IGF -1水平平均为 62 5.2 8± 85.56ng/ml,比对照母羊低 (P <0 .0 5)。本研究提示妊娠后期绵羊母体血浆高水平的IGF -1可能与胎儿生长发育有关 ;胆酸负荷可能影响了妊娠母体的肝功能或胎盘的调节作用     

Comparison of four methods of estimating glomerular filtration rate in cats

Four methods of evaluating renal function were performed in 6 cats anesthetized with halothane in oxygen. Glomerular filtration rate (GFR) was measured simultaneously in each cat by exogenous creatinine clearance (ECC), bolus inulin clearance, and 99mTc(Sn)-diethylene-triaminepentaacetic acid (DTPA) clearance determined by 2 different methods. In the first DTPA clearance method (DTPA-1), we measured radioactivity in serial blood specimens to construct plasma disappearance curves for calculation of GFR. In the second DTPA clearance method (DTPA-2), we used serial external head counts of radioactivity and a single blood specimen to construct plasma disappearance curves for calculation of GFR. Bolus inulin clearance was calculated from plasma disappearance curves using a 1-compartment open pharmacokinetic model (IN-1) and a 2-compartment open pharmacokinetic model (IN-2). Glomerular filtration rates were measured over 3 hours, for creatinine and DTPA methods, and over 4 hours for the inulin methods. The GFR obtained with the reference method (ECC) was 2.56 +/- 0.61 ml/min/kg of body weight (mean +/- SD). Values for GFR determined by ECC and DTPA-1 were significantly correlated (r = 0.852; P less than or equal to 0.05). Correlation between ECC and DTPA 2 was not as good (r = 0.783; P less than or equal to 0.10), but the 2 DTPA methods significantly correlated with one another (r = 0.897; P less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Circadian profile and production rate of melatonin in the cow

Five adult pasture-bred French Friesian cows were used to qualify the circadian profile and characterized pulsatility of plasma melatonin, and to estimate melatonin secretion rate, around the summer solstice. Plasma concentrations of melatonin were low (5 pg/ml) during the photophase, began to rise at sunset (light intensity less than 20 lx) and reached a maximum (about 90 pg/ml) in the middle of the scotophase. The mean amplitude of peaks was 48.67 +/- 23.01 pg/ml, their mean duration was 32.30 +/- 21.50 min and the frequency was 1.5 +/- 0.3 peak/hr during the secretory period (537 +/- 42.3 min). The plasma clearance (ClB) was 0.0247 +/- 0.0013 1/kg per min, the steady state volume of distribution (Vss) was 1.404 +/- 0.225 1/kg, the elimination half life (t1/2 beta) was 66.66 +/- 11.30 min, the mean residence time was 51.37 +/- 9.92 min and the mean production rate was 399.9 +/- 57.37 ng/kg per 24 hr. These results support the concept of linearity for melatonin kinetics in cattle and the plasma clearance value suggest a first-pass hepatic effect.     

Evaluation of a single injection of 99mTc-labeled diethylenetriaminepentaacetic acid for measuring glomerular filtration rate in horses.

Glomerular filtration rate (GFR) was measured in 12 clinically normal horses, using the standard inulin clearance method, and values were compared with values for 2 methods, using a single rapid IV injection of 99mTc-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). The first 99mTc-DTPA method used a 2-compartment model to calculate GFR blood clearance of the tracer. The second method used sequential digital gamma camera images of the kidneys to determine fractional accumulation of the total dose of the tracer in the kidneys (percentage of injected dose, gamma camera) from 0 to 10 minutes after radionuclide administration. Linear correlation among the 3 methods was determined. Mean (+/- SD) GFR, using the inulin clearance method, was 154.67 +/- 42.28 ml/min/100 kg of body weight. Mean GFR, using the 2-compartment blood clearance curve, was 146.92 +/- 27.49 ml/min/100 kg. Mean GFR, using percentage of injected dose (gamma camera method) was 154.7 +/- 22.00 ml/min/100 kg. The percentage of injected dose (gamma camera method) did not correlate significantly to the inulin clearance results. However, a significant (r = 0.666, P less than 0.018) correlation was observed between the inulin method and the 99mTc-DTPA blood clearance method. Significant (P less than 0.0001) difference also was observed in the split function of the equine kidneys, with GFR of the right kidney contributing 60.1 +/- 9.12% of the total function, as determined by 99mTc-DTPA gamma camera imaging. Because the 99mTc-DTPA blood clearance method does not require urine collection, it may be a more practical procedure to measure GFR in the horse.     

Pharmacokinetics and renal clearance of ampicillin in sheep

Pharmacokinetics and renal clearance of ampicillin were investigated in 13 sheep, following one single oral dose of 750 mg. A peak concentration in plasma 0.38 +/- 0.04 microgram/ml (mean +/- SEM) was achieved 95.3 +/- 5.95 min after drug administration. Absorption half-life was 44.4 +/- 4.4 min. The area under the plasma concentration curve was 94.6 +/- 4.5 micrograms.hour.ml-1, while in the case of urine it was 370.5 +/- 28.3 micrograms.hour.ml-1. Biological half-life of ampicillin was 110 +/- 3 min, with an elimination rate constant of 0.0064 +/- 0.0002 min-1. The values for volume of distribution and total body clearance were 8.2 +/- 0.71/kg or 52.0 +/- 4.2 ml/kg/min, respectively. The priming and maintenance doses, using MIC as 0.05 microgram/ml, were suggested to be 8.8 or 8.4 mg/kg, respectively, at an 8-h interval. For MIC of 0.5 microgram/ml, this dose should be 10 times higher. Renal clearance of ampicillin seemed to involve active tubular secretion. Renal excretion indicated either extensive metabolism or excretion through routes other than kidneys.     

Quantitative urinalysis in kittens from four to thirty weeks after birth.

To evaluate renal function and obtain reference values for measurements of urinary excretion of various substances, quantitative urinalysis was performed in healthy, growing kittens from 4 to 30 weeks after birth. Endogenous creatinine clearance, 24-hour urine protein excretion, and urine protein-to-creatinine ratio were determined. Additionally, fractional excretion to creatinine clearance was calculated for calcium, inorganic phosphorus, sodium, potassium, and chloride. Mean +/- SD endogenous creatinine clearance values (range, 3.80 +/- 0.48 to 4.74 +/- 0.61 ml/min/kg) were significantly (P less than 0.0001) higher in kittens 9 to 19 weeks old, compared with younger (range, 1.39 +/- 0.85 to 3.59 +/- 0.86 ml/min/kg) and older kittens (range, 2.69 +/- 0.40 to 3.46 +/- 0.37 ml/min/kg). Mean values for all kittens for 24-hour urine protein excretion (range, 2.54 +/- 1.81 mg/kg at 4 weeks to 11.39 +/- 7.61 mg/kg at 14 weeks) and for urine protein-to-creatinine ratio (range, 0.14 +/- 0.03 to 0.34 +/- 0.18) varied from week to week of age. The urine protein-to-creatinine ratio in kittens greater than or equal to 9 weeks old correlated well (R2 = 0.861) with 24-hour urine protein excretion. Urinary fractional excretion of calcium, inorganic phosphorus, sodium, potassium, and chloride in kittens varied among age groups, being significantly (P less than 0.01) different for potassium and calcium in young kittens (4 to 6 weeks) and older kittens (greater than or equal to 7 weeks).     

The effects of ambient temperature on amikacin pharmacokinetics in gopher tortoises

The pharmacokinetics of amikacin were compared in two groups of tortoises, one held at 20 degrees C and the other at 30 degrees C. The mean (+/- SD) residence time for amikacin in the 30 degrees C tortoises was 22.67 +/- 0.50 h; significantly (P less than 0.05) less than those held at 20 degrees C (41.83 +/- 3.23 h). There was no significant difference (P greater than 0.05) in the steady-state volume of distribution (Vd(ss] between the tortoises held at 30 degrees C (0.241 +/- 0.520 l/kg) and those held at 20 degrees C (0.221 +/- 0.019 l/kg). The clearance rate was faster (P less than 0.05) in the warmer tortoises (10.65 +/- 2.42 ml/min/kg at 30 degrees C compared to 5.27 +/- 0.152 ml/min/kg at 20 degrees C). These data indicate that while the volume of distribution was approximately the same, amikacin remained in the colder tortoises longer because of its slower elimination. The oxygen consumption and metabolism were measured and found to be lower in the colder tortoises, almost by the same 2:1 ratio as clearance time (Cl), mean residence time (MRT), and area under the curve (AUC). The data derived from this limited study indicated that an appropriate therapeutic dosage regimen for amikacin in gopher tortoises at 30 degrees C is 5 mg/kg given i.m. every 48 h.     

Use of the double-isotope single-injection method for estimating renal function in normal cross-bred swine

The double-isotope single-injection method to estimate renal function which utilizes the radiolabeled chemicals [131I]sodium iodohippurate and [125I]sodium iothalamate was evaluated in swine. A total of 46 normal, cross-bred swine were used to determine the applicability of this method for measuring the glomerular filtration rate and effective renal plasma flow. The mean glomerular filtration rate in pigs was determined to be 5.33 +/- 0.82 ml/kg of body weight/minute for [125I]sodium iothalamate with a biological half-life (T 1/2) of 39.18 +/- 7.44 minutes. The mean effective renal plasma flow was determined to be 19.25 +/- 3.12 ml/kg of body weight/minute for [313I]sodium iodohippurate, with a T 1/2 of 18.45 +/- 1.74 minutes. These values are more closely related to the glomerular filtration and effective renal plasma flow values reported for dogs and cats than they are to values reported for man. The method is rapid and reliable; results are available 6 to 8 hours after the experiment. This method is advantageous when information about renal function variables is a prerequisite to pharmacokinetic or toxicologic studies.