Simplified methods for estimation of 99mTc-pentetate and 131I-orthoiodohippurate plasma clearance in dogs and cats

The purpose of this study was to evaluate simplified methods for estimation of Technetium Tc 99m (99mTc)-pentetate and orthoiodohippurate I 131 (131I-OIH) plasma clearance in dogs and cats with 1 and 2 blood samples. Plasma clearances were calculated after a bolus injection of 1.85-11.1 MBq of 99mTc-pentetate and 131I-OIH with a 2-compartment model based on a 12-point curve as a reference method in 21 dogs and 18 cats. Three 2-sample and 3 single-sample methods were investigated. The method yielding the smallest standard deviation of the difference between the reference method and the simplified method was selected as the optimal one. Linear regression analysis was performed between the reference method and the simplified method and coefficient of determination (R2) was calculated. For 99mTc-pentetate plasma clearance, the optimal 2-sample method was the one with a mono-compartment model with samples taken at specific times. For 131I-OIH plasma clearance, the estimation was improved slightly by raising the clearance calculated with a mono-compartment model to the power of an empirically determined parameter. The optimal single-sample method was the one with a linear quadratic regression between the volume of distribution of the tracer at a specific time and the clearance calculated with 12 samples. Two-sample methods performed significantly better than did single-sample methods. The conclusion is made that 99mTc-pentetate and 131I-OIH plasma clearances can be estimated in dogs and cats with 1 or 2 blood samples with a reasonable margin of error compared to plasma clearances calculated with a 2-compartment model and 12 blood samples.     

Simplified methods for estimation of plasma clearance of iohexol in dogs and cats

The purpose of this study was to evaluate simplified methods for iohexol plasma clearance estimation in dogs and cats. Serial blood samples were taken before and 5, 20, 40, 60, 80, 100, 120, 150, 180, and 240 minutes after a bolus injection of iohexol in 51 dogs and 25 cats. Iohexol plasma concentration was determined with X-ray fluorescence. Clearance was calculated by dividing the injected dose by the area under the plasma tracer elimination curve estimated with a 2-compartment pharmacologic model. Clearance was normalized to body surface area (BSA). The 10-point clearance was used as a reference for the evaluation of simplified methods. A 2-sample method based on a single exponential fit and a single-sample method based on a linear quadratic model were investigated. Simplified methods were evaluated by calculating the standard deviation of the difference (SDD) between the clearances obtained with the simplified methods and the 10-point reference method. All combinations of sampling times were evaluated. The best sampling times were chosen for dogs and cats as the ones yielding the lowest SDD. Linear regression analysis was performed between the reference method and the optimized simplified methods. The best combination of time for the 2-sample method was 5 and 120 minutes in dogs and 20 and 180 minutes in cats. The best time for sampling in the single-sample method was 120 minutes in dogs and 80 minutes in cats. Plasma clearance of iohexol can be estimated in dogs and cats from 1 or 2 blood samples with a reasonable margin of error.     

Measurement of glomerular filtration rate via urinary clearance of inulin and plasma clearance of technetium Tc 99m pentetate and exogenous creatinine in dogs

OBJECTIVE: To compare glomerular filtration rate (GFR) measured via urinary clearance of inulin (UCI) with plasma clearance of technetium Tc 99m pentetate (99mTc-pentetate) and creatinine in dogs. ANIMALS: 6 healthy Beagles and 18 Beagles with reduced renal function. PROCEDURE: 13 blood samples were obtained between 5 and 600 minutes after i.v. bolus injections of (99m)Tc-pentetate and creatinine. Plasma clearance of (99m)Tc-pentetate was computed on the basis of 1, 2, or 13 samples, and plasma clearance of creatinine was computed on the basis of 2, 5, or 13 samples. During plasma clearance procedures, constant i.v. infusion of carboxyl carbon 14 inulin was begun and UCI was determined in urine collected from 90 to 120, 120 to 180, and 180 to 240 minutes. Clearance procedures were repeated in 12 dogs to evaluate reproducibility of results. RESULTS: Significant association between UCI and plasma clearance was determined via all methods. However, plasma clearances were moderately to markedly different from UCI, depending on test substance, GFR, and sample numbers used for plasma clearance computations. Comparisons were particularly discordant when some methods of limiting samples were used to define plasma clearance. CONCLUSIONS AND CLINICAL RELEVANCE: Values derived from plasma clearance methods for (99m)Tc-pentetate and creatinine were not interchangeable with UCI results, which raises questions about their reliability as clinical research tools for measurement of GFR. Plasma clearance methods that are relative indices of renal function should not be interpreted as accurate measures of GFR without validation.     

Use of plasma clearance of technetium Tc 99m pentetate to estimate renal clearance during postnatal development in pigs

OBJECTIVE: To compare renal clearance of technetium Tc 99m pentetate with plasma clearance by use of a glomerular filtration rate technique in pigs from 3 to 24 weeks of age. Animals: 24 female pigs. Procedure: At the time of investigation, 5 pigs were 3 weeks old, 6 pigs were 6 weeks old, 8 pigs were 12 weeks old, and 5 pigs were 24 weeks old. Plasma clearance of technetium Tc 99m pentetate was measured by the use of a single injection technique followed by collection of multiple blood samples until 5 hours after the injection. Simultaneously, urine was collected through a urinary catheter, and the renal clearance of technetiumTc 99m pentetate was calculated. Plasma clearance of technetium Tc 99m pentetate was correlated with the renal clearance (r = 0.95). Plasma clearance was higher than renal clearance at all ages (mean, 5.8%), indicating extrarenal clearance of technetium Tc 99m pentetate or methodologic errors. Volume of distribution increased with increasing age but decreased as a fraction of body weight. CONCLUSIONS: Plasma clearance of technetium Tc 99m pentetate estimates renal clearance with acceptable precision when using single injection technique and multiple biood samples in pigs from 3 to 24 weeks of age.     

Evaluation of renal function in cats, using quantitative urinalysis

Two consecutive 24-hour quantitative urinalyses were performed on each of 12 healthy adult cats to evaluate the technique and obtain reference values for measurements of urinary excretion of several substances. Endogenous creatinine clearance (2.31 +/- 0.47 ml/min/kg) and urinary protein excretion (17.43 +/- 9.05 mg/kg/day) were determined. Additionally, clearances and ratios to creatinine clearances were calculated for phosphate, sodium, potassium, and chloride. The endogenous creatinine clearance value was compared with another estimate of glomerular filtration rate that was based on 99mTc(Sn) diethylene-triaminepentaacetic acid clearance (2.52 +/- 0.58 ml/min/kg). Evaluation of feline renal function, using 24-hour quantitative urinalysis techniques, has potential for clinical application, but has several important limitations as well.     

Plasma exogenous creatinine clearance test in dogs: comparison with other methods and proposed limited sampling strategy

Plasma clearance of creatinine was evaluated for assessment of glomerular filtration rate (GFR) in dogs. In 6 healthy dogs (Experiment 1), we determined 24-hour urine clearance of endogenous creatinine, plasma, and urine clearances of exogenous creatinine administered at 40, 80, and 160 mg/kg in a crossover design (linearity study), plasma iothalamate clearance, and plasma and urine clearances of 14C-inulin. In Experiment 2, plasma creatinine and iothalamate clearances were compared, and a linearity study was performed as for Experiment 1 in 6 dogs with surgically induced renal impairment. Experiment 3 compared plasma creatinine clearance with plasma iothalamate clearance before and 3 weeks after induction of moderate renal impairment in 6 dogs. Plasma creatinine clearances were calculated by both noncompartmental and compartmental analyses. In Experiment 1, plasma inulin clearance was higher (P < .001) than other clearance values. Plasma creatinine clearances at the 3 dose rates did not differ from urine inulin clearance and each other. In Experiment 2, plasma creatinine clearances were about 14% lower than plasma iothalamate clearance (P < .05). In Experiment 3, decreases in GFR assessed by plasma clearances of iothalamate and creatinine were similar. Renal failure decreased the daily endogenous input rate of creatinine by 25%. Limiting sampling strategies for optimizing GFR calculation were proposed, allowing an error lower than 6.5% with 4 blood samples. These results suggest that determination of plasma creatinine clearance by a noncompartmental approach offers a reliable, inexpensive, rapid, and convenient means of estimating GFR in routine practice.     

A single sample method for evaluating 51chromium-ethylene diaminic tetraacetic acid clearance in normal and hyperthyroid cats.

BACKGROUND: Chronic kidney failure is frequently seen in middle-aged and elderly cats. 51Chromium-ethylene diaminic tetraacetic acid (51Cr-EDTA) clearance and single blood sample (SBS) method are used in several species to estimate the glomerular filtration rate (GFR). HYPOTHESIS: The hypothesis of this study was that 51Cr-EDTA clearance could be determined using an SBS method in normal and hyperthyroid cats. ANIMALS: Forty-six cats were included in this study, with an average age of 9.5 years. Of these cats, 27 had hyperthyroidism; 19 were healthy. METHODS: After IV injection of 51Cr-EDTA (average dose: 4.25 MBq), 7 blood samples were obtained between 5 and 240 minutes. Reference clearance was calculated in mL/min and mL/min/kg body weight, using a 2-compartment model. Optimal time for clearance measurement with SBS was then determined by systematically comparing each individual plasma concentration to the reference multisample clearance. RESULTS: The average reference plasma clearance of 51Cr-EDTA for all cats was 14.9 mL/min (3.7 mL/min/kg). The clearance in hyperthyroid cats averaged 16.4 mL/min (4.3 mL/min/kg) and in normal cats averaged 10.3 mL/min (2.4 mL/min/kg). The optimal time for the SBS was 48 minutes after injection of tracer 51Cr-EDTA (R2= 0.9414), giving the following converting equation: clearance = (0.0066 x DV48 minutes) - 0.9277 (in mL/min). CONCLUSIONS AND CLINICAL IMPORTANCE: In this study, the single sample 51Cr-EDTA clearance method was used to estimate the global GFR in cats. The method identified differences in clearance between normal and hyperthyroid cats. The optimal time for an SBS was 48 minutes.     

Evaluation of a modified exogenous creatinine clearance as a suitable renal function test for the small animal practice

A suitable method in the routine veterinary practice for the quantitative determination of the glomerular filtration rate (GFR) in dogs and cats has not been available until to date. Therefore, we modified the known plasma clearance model (=P-CL). The resulting P-CLterminal was assessed concerning its diagnostic value. P-CL of exogenous creatinine (P-CLcrea) and of inulin were determined in dogs (n=12, Beagle, 6 months of age) and cats (n=11, Domestic Short Hair, 14 months of age). The marker substances were administered as a bolus injection. In fasted dogs, P-CLcrea was 84.3 +/- 14.85 ml/min/m2 after a creatinine dose of 2.4 g/m2. An electrolyte infusion during the clearance determination did not alter the resulting values (p>0.05). In fasted cats, P-CLcrea was 54.7 +/- 5.8 ml/min/m2 (creatinine dose 2.0 g/m2). The inulin clearance, determined at the same time, was 104.5 +/- 19.81 ml/min/m2. Feeding the cats just before and during the test increased P-CL of both markers significantly (p<0.05). In order to adapt the clearance method for diagnostic assessment of GFR in the small animal practice, we aimed at minimizing the number of required blood samples (3 instead of 7 or more) and introduced the modified exogenous creatinine clearance (P-CLterminal). These values determined were 108.4 +/- 20.81 ml/min/m2 in fasted dogs and 66.3 +/- 11.81 ml/min/m2 in fasted cats. An electrolyte infusion (dogs) and feeding (cats) had the same effect on P-CLterminal values as described above for P-CL. In conclusion,the modified exogenous creatinine clearance is a suitable renal function test for the early diagnosis of renal disease in dogs and cats presented in small animal practices.     

Effects of administration of fluids and diuretics on glomerular filtration rate, renal blood flow, and urine output in healthy awake cats

OBJECTIVES: To determine effects of commonly used diuretic treatments on glomerular filtration rate (GFR), renal blood flow (RBF), and urine output (UO) and compare 2 methods of GFR measurement in healthy awake cats. ANIMALS: 8 healthy cats. PROCEDURE: In a randomized crossover design, cats were randomly allocated to 4 groups: control; IV administration of fluids; IV administration of fluids and mannitol; and IV administration of fluids, dopamine, and furosemide. Inulin and para-aminohippuric acid were used for determination of plasma clearance for GFR and RBF, respectively. Plasma clearance of technetium-Tc-99m-diethylenetriaminepentacetic acid (99mTc-DTPA) was also used for GFR determination. RESULTS: Furosemide-dopamine induced the largest UO, compared with other groups. Both mannitol and fluid therapy increased RBF, compared with the control group. Mannitol, and not fluid therapy, increased RBF, compared with furosemide-dopamine. There were significant differences in GFR values calculated from 99mTc-DTPA and inulin clearances between the 2 groups. In all groups, use of 99mTc-DTPA caused underestimation of GFR, compared with use of inulin. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy awake cats, administration of furosemide-dopamine did not increase GFR or RBF despite increased UO. Fluid therapy and fluid therapy plus mannitol improved RBF. Determination of GFR by use of 99mTc-DTPA cannot always be substituted for inulin clearance when accurate measurement is required.     

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.     

A Single Sample Method for Evaluating 51Chromium-Ethylene Diaminic Tetraacetic Acid Clearance in Normal and Hyperthyroid Cats

Background: Chronic kidney failure is frequently seen in middle-aged and elderly cats. ⁵¹Chromium-ethylene diaminic tetraacetic acid (⁵¹Cr-EDTA) clearance and single blood sample (SBS) method are used in several species to estimate the glomerular filtration rate (GFR).
Hypothesis: The hypothesis of this study was that ⁵¹Cr-EDTA clearance could be determined using an SBS method in normal and hyperthyroid cats.
Animals: Forty-six cats were included in this study, with an average age of 9.5 years. Of these cats, 27 had hyperthyroidism; 19 were healthy.
Methods: After IV injection of ⁵¹Cr-EDTA (average dose: 4.25 MBq), 7 blood samples were obtained between 5 and 240 minutes. Reference clearance was calculated in mL/min and mL/min/kg body weight, using a 2-compartment model. Optimal time for clearance measurement with SBS was then determined by systematically comparing each individual plasma concentration to the reference multisample clearance.
Results: The average reference plasma clearance of ⁵¹Cr-EDTA for all cats was 14.9 mL/min (3.7 mL/min/kg). The clearance in hyperthyroid cats averaged 16.4 mL/min (4.3 mL/min/kg) and in normal cats averaged 10.3 mL/min (2.4 mL/min/kg).
The optimal time for the SBS was 48 minutes after injection of tracer ⁵¹Cr-EDTA ( R ²= 0.9414), giving the following converting equation: clearance = (0.0066 × DV_{48 minutes}) – 0.9277 (in mL/min).
Conclusions and Clinical Importance: In this study, the single sample ⁵¹Cr-EDTA clearance method was used to estimate the global GFR in cats. The method identified differences in clearance between normal and hyperthyroid cats. The optimal time for an SBS was 48 minutes.     

Relationship between plasma iohexol clearance and urinary exogenous creatinine clearance in dogs

The objective of this study was to determine if plasma iohexol clearance, computed by a 1-compartment model defined by 3 plasma samples. was an accurate measure of glomerular filtration rate (GFR) in dogs. Twenty-two adult Beagle dogs of both genders were studied. Ten dogs had intact kidneys, and 12 dogs had surgically reduced renal mass. A bolus injection of iohexol was made, and blood was obtained for plasma iohexol assay after 120, 180, and 240 minutes. Plasma was analyzed for iohexol concentration by means of 3 assay methods: chemical, high-performance liquid chromatography (HPLC), and inductively coupled plasma emission spectroscopy (ICP). Urinary clearance of exogenous creatinine was used to measure GFR for three 30-minute periods occurring between 150 and 240 minutes after iohexol injection. Plasma clearance of iohexol and renal clearance of creatinine were compared by linear regression analysis and by limits of agreement techniques. Plasma iohexol clearance and urinary exogenous creatinine clearance were significantly correlated (chemical R2 = .90; HPLC R2 = .96; and ICP R2 = .96). The 1-compartment iohexol clearance:exogenous creatinine clearance ratios were 1.04 +/- 0.17, 1.05 +/- 0.14, and 1.10 +/- 0.15 for the chemical, HPLC, and ICP methods of assay, respectively, indicating that plasma iohexol clearance slightly overestimated GFR. Assuming a +/- 2 standard deviation interval for error, corrected plasma iohexol clearance measured GFR with +/-34% accuracy for the chemical, +/-26% accuracy for the HPLC, and +/-27% accuracy for the ICP method. These results indicate that plasma iohexol clearance should have utility for detection of renal dysfunction earlier in the course of progressive renal disease than is possible with measurement of plasma creatinine or urea concentrations.     

IOHEXOL PLASMA CLEARANCE IN HEALTHY DOGS AND CATS

Iohexol plasma clearance as a measure of glomerular filtration was determined in 31 dogs and 19 cats after an intravenous (i.v.) bolus injection. All animals were healthy and privately owned. Serial blood samples were taken before and up to 4 h after tracer injection. Iohexol plasma concentration was determined using X-ray fluorescence. A plasma tracer elimination curve was generated and clearance was calculated by dividing the injected dose by the area under the curve estimated using a two-compartment pharmacological model. Clearance was normalized to body weight (BW), body surface area (BSA), and extracellular fluid volume (ECFV). Mean, SD, and coefficient of variation of plasma clearance, before and after normalization, were calculated. Linear regression analyses were performed between body size and normalized plasma clearances. No significant linear relation was found between BSA and clearance normalized to BSA in dogs, and between BSA, BW, ECFV and clearance normalized to BSA, BW, and ECFV in cats. The optimal method for normalization of iohexol plasma clearance in dogs was by using BSA. In cats, all three methods tested were considered satisfactory. Normalization to BSA appears to be superior to normalization to BW and ECFV in dogs, and can be recommended for clinical use.     

The Clearance of Creatinine, Inulin, Para-aminohippurate and Phenosulphothalein in the Cat

Endogenous creatinine, inulin, para-amino-hippurate and phenolsulphothalein clearances for healthy cats are presented. The values for inulin and para-aminohippurate clearances (ml/kg/min) are similar to those for the dog. Creatinine clearance was less than inulin clearance values. Pnenolsulphothalein clearance may be a better index of glomerular rather than tubular function in the cat.     

Effects of theophylline on tracheal mucociliary clearance rates in healthy cats

OBJECTIVE: To determine tracheal mucociliary clearance rate (TMCCR) by use of a standard protocol in healthy anesthetized cats and to determine the effect of theophylline on TMCCR in healthy anesthetized cats. ANIMALS: 6 healthy cats. PROCEDURE: Cats were anesthetized with propofol, and a droplet of the radiopharmaceutical technetium Tc 99m macroaggregated albumin was placed endoscopically at the carina. Dynamic acquisition scintigraphic imaging was performed, using the larynx as the end point. The TMCCR was determined by measuring the distance the droplet traveled by frame rate. Each cat was imaged 6 times as follows: 3 times following placebo administration and 3 times following the administration of sustained release theophylline (25 mg/kg, PO). Serum theophylline concentrations were assessed during imaging to ensure therapeutic concentrations. RESULTS: The TMCCR in healthy adult cats anesthetized with propofol was 22.2 +/- 2.8 mm/min. Tracheal mucociliary clearance rate in cats receiving theophylline was 21.8 +/- 3.5 mm/min. Theophylline administration did not significantly alterTMCCR. CONCLUSIONS AND CLINICAL RELEVANCE: Theophylline has been shown to increase TMCCR in humans and dogs. In our study, we determined TMCCR in healthy anesthetized cats and found that it was not accelerated by the administration of theophylline.     

Evaluation of iohexol clearance used to estimate glomerular filtration rate in clinically normal foals

OBJECTIVE: To determine whether pharmacokinetic analysis of data derived from a single i.v. dose of iohexol could be used to predict creatinine clearance and evaluate simplified methods for predicting serum clearance of iohexol with data derived from 2 or 3 blood samples in clinically normal foals. ANIMALS: 10 healthy foals. PROCEDURE: Serum disposition of iohexol and exogenous creatinine clearance was determined simultaneously in each foal (5 males and 5 females). A 3-compartment model of iohexol serum disposition was selected via standard methods. Iohexol clearance calculated from the model was compared with creatinine clearance. Separate limited-sample models were created with various combinations of sample times from the terminal slope of the plasma versus time profile for iohexol. Correction factors were determined for the limited-sample models, and iohexol clearance calculated via each method was compared with exogenous creatinine clearance by use of method comparison techniques. RESULTS: Mean exogenous creatinine clearance was 2.17 mL/min/kg. The disposition of iohexol was best described by a 3-compartment open model. Mean clearance value for iohexol was 2.15 mL/min/kg and was not significantly different from mean creatinine clearance. A method for predicting serum iohexol clearance based on a 2-sample protocol (3- and 4-hour samples) was developed. CONCLUSIONS AND CLINICAL RELEVANCE: Iohexol clearance can be used to predict exogenous creatinine clearance and can be determined from 2 blood samples taken after i.v. injection of iohexol. Appropriate correction factors for adult horses and horses with abnormal glomerular filtration rate need to be determined.     

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.     

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)     

Pharmacokinetics of procainamide hydrochloride in dogs

Pharmacokinetics of procainamide hydrochloride were studied in 2 groups of dogs. In a group of 6 dogs, procainamide was administered IV at a small dose of 8 mg/kg (group 1), and blood samples were obtained for 3.5 hours. In another group of 6 dogs, procainamide was administered IV and orally at an average dose of 25.5 mg/kg (group 2) in a crossover manner. Blood samples were obtained for 48 hours. In 2 dogs (previously used in part II), N-acetylprocainamide (NAPA) was administered IV at a dose of 10 mg/kg. Plasma samples were assayed for procainamide by fluorescence polarization immunoassay, and NAPA samples were assayed by high-performance liquid chromatography. In group 1, the elimination of procainamide was described by a 1-compartment, open pharmacokinetic model. The elimination half-life was 2.43 hours, the apparent volume of distribution was 1.44 L/kg, and the systemic clearance was 0.412 L/kg/hr. In group 2, 2 of the 6 dogs were described by a 1-compartment model, and 4 of the 6 dogs were described with a 2-compartment pharmacokinetic model. The elimination half-life for the IV dosage was 2.85 hours, the apparent volume of distribution was 2.13 L/kg, and the systemic clearance was 0.519 L/kg/hr. For the orally administered dose, the bioavailability was 85%, and the absorption half-life was 0.5 hours. There was no evidence of acetylation of procainamide to NAPA or deacetylation of NAPA to procainamide. The estimated elimination half-life of NAPA was 4.7 hours.