The Effect of Experimental Renal Failure on Tolfenamic Acid Disposition in the Dog

Lefebvre, Henri; Laroute, Valérie; Alvinerie, M.; Schneider, Marc; Vinclair, P.; Braun, Jean‐Pierre; Toutain, Pierre‐Louis

doi:10.1002/(sici)1099-081x(199701)18:1<79::aid-bdd34>3.0.co;2-f

Cited by 25 publications

(34 citation statements)

References 9 publications

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“…The results of this study demonstrate that plasma exogenous creatinine clearance is an accurate indicator of GFR in healthy dogs and dogs with a 60% decrease in GFR over a creatinine dosage range of 40-160 mg/kg. Previous values observed in healthy dogs for clearance of endogenous creatinine (3.7 Ϯ 0.77 mL/kg/min), 14 plasma iothalamate (2.9 Ϯ 0.26 mL/kg/min), 2 plasma inulin (4.4 Ϯ 1.15 mL/ kg/min), 15 and urine inulin (2.8 mL/kg/min) 16 are similar to those observed in the dogs of this study. Mean recovery of exogenous creatinine in canine urine was about 99% (similar to values previously published), 17 indicating that extrarenal elimination of creatinine is negligible.…”

Section: Discussionsupporting

confidence: 88%

Plasma Exogenous Creatinine Clearance Test in Dogs: Comparison with Other Methods and Proposed Limited Sampling Strategy

Watson

Lefebvre

Concordet

et al. 2002

Veterinary Internal Medicne

Self Cite

111

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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 14 C-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 Ͻ .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 Ͻ .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.

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Section: Discussionsupporting

confidence: 88%

Plasma Exogenous Creatinine Clearance Test in Dogs: Comparison with Other Methods and Proposed Limited Sampling Strategy

Watson

Lefebvre

Concordet

et al. 2002

Veterinary Internal Medicne

Self Cite

111

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“…In the absence of DPC 333, the renal clearance of MTX in beagle dogs (from 0 to 48 h) was 1.8 Ϯ 0.1 ml/min/kg. With correction for canine plasma protein binding (36.9%) (Lui et al, 1985), the renal clearance of MTX (2.9 Ϯ 0.2 ml/min/kg) was lower than the glomerular filtration rate determined in beagle dogs (4.4 Ϯ 1.2 ml/min/kg) using inulin (Lefebvre et al, 1997). Our observation indicates that active renal tubular reabsorption of MTX is significant in dogs, consistent with a previous report (Huang et al, 1979).…”

Section: Discussionmentioning

confidence: 99%

Effect of DPC 333 [(2R)-2-{(3R)-3-Amino-3-[4-(2-methylquinolin-4-ylmethoxy)phenyl]-2-oxopyrrolidin-1-yl}-N-hydroxy-4-methylpentanamide], a Human Tumor Necrosis Factor α-Converting Enzyme Inhibitor, on the Disposition of Methotrexate: A Transporter-Based Drug-Drug Interaction Case Study

Luo

Garner

Xiong³

et al. 2007

Drug Metab Dispos

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DPC 333 [(2R)-2-{(3R)-3-amino-3-[4-(2-methylquinolin-4-ylmethoxy)phenyl]-2-oxopyrrolidin-1-yl}-N-hydroxy-4-methylpentanamide]is a potent human tumor necrosis factor ␣-converting enzyme inhibitor with potential therapeutic implications for rheumatoid arthritis. Methotrexate (MTX), a drug for the treatment of rheumatoid arthritis, is eliminated primarily unchanged via renal and biliary excretion in humans as well as in rats and dogs. The objective of the present study was to investigate the potential effect of DPC 333 on the disposition of MTX. In dogs, DPC 333 administered orally at 1.7 mg/kg 15 min before the intravenous administration of [ MTX, a bicarboxylic acid (Fig. 1) structurally similar to folic acid, has been used for the treatment of rheumatoid arthritis at low doses (Weinblatt et al., 1985;Schnabel and Gross, 1994). MTX is minimally metabolized to 7-hydroxy MTX in vivo, whereas most MTX is eliminated as intact drug via renal and biliary excretion in humans (Henderson et al., 1965b;Lui et al., 1985;Nuernberg et al., 1990;Seideman et al., 1993;Chladek et al., 1998), and in the preclinical species including mice, rats, dogs, and monkeys (Henderson et al., 1965a;Steinberg et al., 1982;Masuda et al., 1997). In mice and rats, the routes of biliary and renal elimination contribute almost equally to the total body clearance of MTX, but in monkeys and humans, renal elimination is more extensive than biliary excretion (Henderson et al., 1965a,b;Steinberg et al., 1982;Williams and Huang, 1982;Nuernberg et al., 1990;Masuda et al., 1997). For example, after intravenous administration, the cumulative biliary excretion of MTX was 44 to 72% of the dose in bile duct-cannulated rats, but only 16% in rhesus monkeys with bile fistula; after intraperitoneal or intravenous administration, MTX recovery in feces was 45% of the dose in rats and 40% in mice, but only 13% in monkeys and 10% in humans. Biliary H.X. and K.L.R.B. were funded in part by Grant R01 GM41935 from the National Institutes of Health.Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

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“…P‐creatinine is more efficient than plasma urea concentration for the diagnosis of CRF 148 . In dogs with spontaneous or surgically‐induced CRF, the correlation between plasma concentrations of urea and creatinine was reported to be high 89,149,164–167 or low 168 . P‐creatinine variations correlated well with the concentration of plasma cystatin C, a small protein that is eliminated only by glomerular filtration 43,169–171 …”

Section: Pathologic Variations In P‐creatininementioning

confidence: 99%

Creatinine in the Dog: A Review

Braun

Lefebvre

Watson

2003

Veterinary Clinical Pathol

186

154

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Creatinine is the analyte most frequently measured in human and veterinary clinical chemistry laboratories as an indirect measure of glomerular filtration rate (GFR). Although creatinine metabolism and the difficulties of creatinine measurement have been reviewed in human medicine, similar reviews are lacking in veterinary medicine. The aim of this review is to summarize information and data about creatinine metabolism, measurement, and diagnostic significance in the dog. Plasma creatinine originates from the degradation of creatine and creatine phosphate, which are present mainly in muscle and in food. Creatinine is cleared by glomerular filtration with negligible renal secretion and extrarenal metabolism, and its clearance is a good estimate of GFR. Plasma and urine creatinine measurements are based on the nonspecific Jaffé reaction or specific enzymatic reactions; lack of assay accuracy precludes proper interlaboratory comparison of results. Preanalytical factors such as age and breed can have an impact on plasma creatinine (P-creatinine) concentration, while many intraindividual factors of variation have little effect. Dehydration and drugs mainly affect P-creatinine concentration in dogs by decreasing GFR. P-creatinine is increased in renal failure, whatever its cause, and correlates with a decrease in GFR according to a curvilinear relationship, such that P-creatinine is insensitive for detecting moderate decreases of GFR or for monitoring progression of GFR in dogs with severely reduced kidney function. Low sensitivity can be obviated by determining endogenous or exogenous clearance rates of creatinine. A technique for determining plasma clearance following IV bolus injection of exogenous creatinine and subsequent serial measurement of P-creatinine does not require urine collection and with additional studies may become an established technique for creatinine clearance in dogs.

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The Effect of Experimental Renal Failure on Tolfenamic Acid Disposition in the Dog

Cited by 25 publications

References 9 publications

Plasma Exogenous Creatinine Clearance Test in Dogs: Comparison with Other Methods and Proposed Limited Sampling Strategy

Plasma Exogenous Creatinine Clearance Test in Dogs: Comparison with Other Methods and Proposed Limited Sampling Strategy

Effect of DPC 333 [(2R)-2-{(3R)-3-Amino-3-[4-(2-methylquinolin-4-ylmethoxy)phenyl]-2-oxopyrrolidin-1-yl}-N-hydroxy-4-methylpentanamide], a Human Tumor Necrosis Factor α-Converting Enzyme Inhibitor, on the Disposition of Methotrexate: A Transporter-Based Drug-Drug Interaction Case Study

Creatinine in the Dog: A Review

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