Characterization of the renal handling of p-aminohippurate (PAH) in the beagle dog (Canis familiaris)

Mann, William A.; Kinter, Lewis B.

doi:10.1016/0306-3623(93)90318-r

Cited by 8 publications

(9 citation statements)

References 8 publications

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“…Although it has been reported that the mRNA expression levels of Oat1 and Oat3 in the kidneys of dogs are low compared with rats , there is no information regarding the protein expression levels of these transporters across the species. On the other hand, it has been reported that renal proximal secretion would be involved in the urinary excretion of PAH in dogs . As reported previously , uptake of PAH in the kidney slices was observed in dogs and the initial uptake clearance of PAH was similar between rats and dogs (Figure ).…”

Section: Discussionsupporting

confidence: 77%

Species differences of organic anion transporters involved in the renal uptake of 4‐amino‐3‐chlorophenyl hydrogen sulfate, a metabolite of resatorvid, between rats and dogs

Takeuchi

Jinno

Ebihara

et al. 2013

Biopharm & Drug Disp

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Previous studies on the metabolic fate of resatorvid (TAK-242) have shown that species differences in the pharmacokinetics of 4-amino-3-chlorophenyl hydrogen sulfate (M-III), a metabolite of TAK-242, between rats and dogs are mainly attributable to the urinary excretion process. In the present study, the renal uptake mechanism of M-III was investigated using kidney slices and Xenopus laevis oocytes expressing rat organic anion transporter 1 (rOat1; Slc22a6) and rOat3 (Slc22a8). The uptake of p-aminohippuric acid (PAH), a substrate for Oats, by kidney slices from rats and dogs increased at 37 °C and M-III inhibited the uptake. The initial uptake clearance of M-III by rat kidney slices was 0.295 and 0.0114 ml/min/g at 37 °C and 4 °C, respectively. The Eadie-Hofstee plot of M-III uptake at 37 °C revealed two-component transport processes with K(m) values being 6.48 and 724 µmol/l. The uptake was inhibited by probenecid (PBC), PAH and benzylpenicillin (PCG). In contrast, in dog kidney slices, the initial uptake clearance of M-III was 8.70 × 10(-3) and 9.00 × 10(-3) ml/min/g at 37 °C and 4 °C, respectively, and the uptake was not inhibited by PBC. Furthermore, rOat1- and rOat3-expressing oocytes mediated M-III uptake and the uptake was inhibited by PAH and PCG, respectively. These results suggest that rOat1 and rOat3 are responsible for the renal uptake of M-III in rats. Moreover, it is speculated that Oat(s) is unable to transport M-III in dogs and that the difference in the substrate recognition of Oat(s) contributes to the species difference in the pharmacokinetics of M-III between rats and dogs.

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Section: Discussionsupporting

confidence: 77%

Species differences of organic anion transporters involved in the renal uptake of 4‐amino‐3‐chlorophenyl hydrogen sulfate, a metabolite of resatorvid, between rats and dogs

Takeuchi

Jinno

Ebihara

et al. 2013

Biopharm & Drug Disp

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“…Anesthesia was induced by propofol 6 mg/kg intravenously (IV) and was maintained by isoflurane. After the initiation of anesthesia, PAH was given IV as a bolus by a priming dose of 6 mg/kg body weight over 5 min followed by constant IV infusion (0.3 mg/kg/min) at a rate of 2 ml/ min in lactated Ringer's solution during experiment [13,19]. Equilibration period of 30 min was allowed after the initiation of PAH infusion.…”

Section: Animalsmentioning

confidence: 99%

Renal Effects of Medetomidine in Isoflurane-Anesthetized Dogs with Special Reference to Its Diuretic Action

Saleh

Aoki

Shimada

et al. 2005

The Journal of Veterinary Medical Science

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ABSTRACT. Renal effects of the selective α 2 -adrenoceptor agonist, medetomidine, were investigated in anesthetized dogs. Animals were administered medetomidine 20 and 40 µg/kg intravenously (IV) and 80 µg/kg intramuscularly (IM) or 1 ml of saline IV. Urine and blood samples were collected before and at 30, 60, 90 and 120 min following medetomidine injection. Mean arterial blood pressure (MABP), renal blood flow (RBF), glomerular filtration rate (GFR), urine volume (U v ), urine osmolality (U osm ), free water clearance (C H2O ), fractional clearance of sodium (F Na ), plasma osmolality (P osm ), plasma glucose levels and plasma antidiuretic hormone (ADH) concentrations were measured. The results showed that IV administration of medetomidine initially increased MABP 5-15 min followed by long-lasting decrease. The initial hypertension was not observed after IM administration, which was accompanied by a more profound hypotensive effects. RBF, GFR, U v , C H2O increased after IV injection and decreased after IM. Medetomidine increased FNa and Posm and decreased U osm . Plasma glucose levels initially increased and subsequently decreased. Plasma ADH concentration was decreased by IV injection but increased by IM administration. Our data imply that: 1) IV administration of medetomidine at dose rates of 20 and 40 µg/kg results in profound diuresis up to 2 hr; 2) Suppression of ADH release from the CNS is one of the mechanisms of medetomidine-induced diuresis although it may not be the principal one. KEY WORDS: anesthesia, canine, isoflurane, medetomidine and renal function.

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“…OATs are ATP‐dependent and can be saturated by PAH as the T m(PAH) is approached. In previous studies, plasma concentrations of PAH above 30 μ g/mL resulted in a fall in the renal clearance of PAH (Mann & Kinter, ). In the largest dog (55 kg body weight) employed in the present study, the plasma steady‐state PAH concentration was 50 μ g/mL, approaching the T m(PAH) .…”

Section: Discussionmentioning

confidence: 99%

“…PAH is an organic anion that is freely filtered by the glomerulus, extensively secreted into the proximal convoluted tubules, and poorly reabsorbed (Mann & Kinter, ). As PAH is removed from the blood by the kidneys and is almost completely removed from renal plasma in one passage through the kidney, the renal clearance of PAH is approximately equal to ERPF (Schnurr et al ., ; Mann & Kinter, ; Toto, ).…”

Section: Discussionmentioning

confidence: 99%

“…This three-fourth power is widely accepted as the theoretical and experimental interspecific mass exponent relating several allometric relationships to body weight, so the similarity of GFR to the three-fourth power suggests that the same factors that drive standard allometry in interspecific comparisons also apply to intraspecific comparisons (West et al, 1997;Mahmood, 2007). PAH is an organic anion that is freely filtered by the glomerulus, extensively secreted into the proximal convoluted tubules, and poorly reabsorbed (Mann & Kinter, 1993). As PAH is removed from the blood by the kidneys and is almost completely removed from renal plasma in one passage through the kidney, the renal clearance of PAH is approximately equal to ERPF (Schnurr et al, 1980;Mann & Kinter, 1993;Toto, 1995).…”

Section: Renal Physiological Parametersmentioning

confidence: 99%

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Anatomical and physiological basis for the allometric scaling of cisplatin clearance in dogs

Achanta

Sewell

Ritchey

et al. 2015

Vet Pharm & Therapeutics

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Cisplatin is a platinum-containing cytotoxic drug indicated for the treatment of solid tumors in veterinary and human patients. Several of the algorithms used to standardize the doses of cytotoxic drugs utilize allometry, or the nonproportional relationships between anatomical and physiological variables, but the underlying basis for these relationships is poorly understood. The objective of this proof of concept study was to determine whether allometric equations explain the relationships between body weight, kidney weight, renal physiology, and clearance of a model, renally cleared anticancer agent in dogs. Postmortem body, kidney, and heart weights were collected from 364 dogs (127 juveniles and 237 adults, including 51 dogs ≥ 8 years of age). Renal physiological and cisplatin pharmacokinetic studies were conducted in ten intact male dogs including two juvenile and eight adult dogs (4-55 kg). Glomerular filtration rate (GFR), effective renal plasma flow, effective renal blood flow, renal cisplatin clearance, and total cisplatin clearance were allometrically related to body weight with powers of 0.75, 0.59, 0.61, 0.71, and 0.70, respectively. The similar values of these diverse mass exponents suggest a common underlying basis for the allometry of kidney size, renal physiology, and renal drug handling.

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Characterization of the renal handling of p-aminohippurate (PAH) in the beagle dog (Canis familiaris)

Cited by 8 publications

References 8 publications

Species differences of organic anion transporters involved in the renal uptake of 4‐amino‐3‐chlorophenyl hydrogen sulfate, a metabolite of resatorvid, between rats and dogs

Species differences of organic anion transporters involved in the renal uptake of 4‐amino‐3‐chlorophenyl hydrogen sulfate, a metabolite of resatorvid, between rats and dogs

Renal Effects of Medetomidine in Isoflurane-Anesthetized Dogs with Special Reference to Its Diuretic Action

Anatomical and physiological basis for the allometric scaling of cisplatin clearance in dogs

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