A method for estimating the glomerular filtration rate in conscious monkeys

Satoh, Hiroshi; Nomiya, Nana; Imai, Daiki; Satō, Shigeru; Sakurai, Katsunobu; Takasuna, Kiyoshi; Furuhama, Kazuhisa

doi:10.1002/jat.3178

Cited by 3 publications

(3 citation statements)

References 21 publications

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“…All female monkeys did not show any abnormal physical appearance or abnormal liver and kidney functions after multiple oral dosing. Constant levels of a plasma kidney marker (creatinine) were in line with those reported in cynomolgus monkeys [38] and humans [39]. A significant elevation of plasma AST level, a liver marker, at 24 h after oral dosing of the vehicle was assumed to indicate the stress effect on animal manipulations during the experiment.…”

Section: Discussionsupporting

confidence: 75%

Comparative Pharmacokinetics of Puerarin Alone and in Pueraria mirifica Extract in Female Cynomolgus Monkeys

et al. 2020

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Pueraria mirifica is an endemic Thai plant that has been used for rejuvenation and in the relief of various aging diseases. Puerarin is one of the major isoflavones found in this plant and shows several pharmacological activities in relation to the Thai traditional use of P. mirifica. Therefore, comparative pharmacokinetics of pure puerarin alone and that in a P. mirifica extract in cynomolgus monkeys were conducted in order to investigate the pharmacokinetic profiles of the 2 preparations. To this end, puerarin and P. mirifica extract, at an equivalent dose of 10 mg/kg of puerarin, were orally dosed to adult female monkeys for 7 consecutive days. A single intravenous injection of puerarin at a dose of 1 mg/kg was also peformed. Serial blood samples and excreta were collected from 0 – 24 h and 0 – 48 h after dosing. Determination of the puerarin levels and its metabolites in biological samples was conducted by liquid chromatography tandem mass spectrometry. Plasma levels of aspartate aminotransferase, alanine aminotransferase, and creatinine fluctuated in the normal range, with no abnormal physical signs in the animal. The absolute oral bioavailability of puerarin was approximately 1% in both preparations. Accumulation of puerarin was found after oral dosing for 7 consecutive days in both groups. Major metabolites of puerarin found in monkeys were hydroxylation and deglycosylation products. A negligible amount of unchanged puerarin was detected in urine and feces. Pharmacokinetic profiles obtained from this study could help to design the prescribed remedy of puerarin and P. mirifica extract phytopharmaceutical products for human use.

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Section: Discussionsupporting

confidence: 75%

Comparative Pharmacokinetics of Puerarin Alone and in Pueraria mirifica Extract in Female Cynomolgus Monkeys

et al. 2020

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“…All female monkeys did not show any abnormal physical appearance or abnormal liver and kidney functions after 7-day repeated oral dosing. Constant levels of a plasma kidney marker (creatinine) were in line with those reported in cynomolgus monkeys (Satoh et al, 2016) and humans (David et al, 2016). A significant elevation of plasma AST level, a liver marker, at 24 h after oral dosing of the vehicle was assumed to indicate the stress effect on animal manipulations during the experiment.…”

Section: Chapter 5 Discussion and Conclusionsupporting

confidence: 84%

Comparative pharmacokinetics of puerarin in pure compound form and puerarin in white kwao krua extract in female cynomolgus monkeys

Namken

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Pueraria mirifica is an endemic Thai plant that puerarin is a major chemical found in this plant and shows several pharmacological activities in aging diseases. Although the pharmacokinetic data on puerarin have been reported in rodents, it is still inconclusive for the development of puerarin as phytopharmaceutical products for human use. This is because of the differences in anatomical and physiological characteristics between rodents and humans. Therefore, the comparative pharmacokinetics of puerarin in pure compound form (PUE) and puerarin in P. mirifica extract (PME) was conducted in female cynomolgus monkeys. PME at a dose of 826 mg/kg.BW (equivalent to 10 mg/kg.BW of puerarin) and PUE at a dose of 10 mg/kg.BW were daily orally administered to monkeys for 7 consecutive days. A single intravenous injection of 1 mg/kg.BW of PUE was also performed for the bioavailability analysis of puerarin orally administered to monkeys. Serial blood samples and excreta (urine and feces) were collected after dosing at designated times. The levels of puerarin in biological samples were determined by liquid chromatography tandem mass spectrometry. After PME and PUE orally dosing to monkeys, plasma levels of aspartate aminotransferase and alanine aminotransferase which were indicated the liver function, and plasma creatinine levels which were indicated the kidney function were fluctuated in the normal range, with no abnormal physical signs in animals. The absolute oral bioavailability of puerarin was 1.44% after the PME oral dosing and 0.88% after the PUE oral dosing, but the T1/2 was prolonged for nearly two times in the PUE group (4.78 h) comparing to the PME group (2.61 h). After 7-day multiple oral dosing of puerarin in both preparations, the accumulations were occurred in the body of the animals. Major metabolite pathways of puerarin found in monkeys were hydroxylation and deglycosylation before excreted via urine and feces. A negligible amount of unchanged puerarin was detected for less than 1% in urine and feces. In conclusion, an oral dosing of a puerarin shows the better absorption in the extract form than in the pure compound form, but it has a shorter half-life. Puerarin can be accumulated in the body of the animals when it is continuously orally dosing. Thus, the pharmacokinetic profiles obtained from female cynomolgus monkeys in this study could help to design the prescribed remedy of the oral administration of puerarin as phytopharmaceutical products for human use.

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“…Estimation of early-stage kidney disease is difficult, as patients are often asymptomatic. Glomerular filtration rate (GFR) is the best overall index of determining kidney function in humans and veterinary species ( 4 , 5 ). Use of endogenous renal filtration markers such as BUN and serum Cr are typically used clinically since these assays are quick, easy, and readily available ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

A New Method for Estimating Glomerular Filtration Rate in Rhesus Macaques (Macaca mulatta)

Tomasino,

Olson,

Schaaf

et al. 2023

Radiation Research

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Late effects of total- or partial-body irradiation include chronic kidney injury (CKI), which increases morbidity and mortality. Glomerular filtration rate (GFR) is the gold standard measure of kidney function. Renal function markers, such as blood urea nitrogen (BUN) and serum creatinine (Cr), may not be higher than reference ranges until 50% or more of nephrons are affected. Currently available methods to measure GFR are difficult and expensive, requiring multiple blood draws or timed urine collections, but their use can provide a framework for the development of simpler GFR estimates. The measurement of iohexol clearance is a validated tool used to determine GFR in veterinary patients. In this study, we aimed to determine if the Schwartz formula as used in human pediatric medicine can estimate GFR in rhesus macaques. We hypothesized that iohexol-GFR would correlate with the Schwartz formula-estimated GFR (eGFR) in irradiated and non-irradiated rhesus macaques. Twelve rhesus macaques [age 5–14 years (mean 7 years); 5 females, 7 males] with a range of BUN levels were selected for comparison to 4 non-irradiated controls (2 females, 2 males). Irradiated animals were divided by BUN into 3 groups: BUN ≤20 mg/dL (n = 4), BUN >20–24 mg/dL (n = 4), and BUN ≥25 mg/dL (n = 4). Baseline serum chemistry and urinalysis were used to assess renal function. For measurement of GFR, macaques were maintained under general anesthesia and received an intravenous injection of iohexol (2 mL/kg, 300 mg I/mL). Whole blood was collected at 10, 30, 60 and 90 min post-iohexol injection. Plasma iohexol concentrations were determined by mass spectrometry. GFR was calculated from the peak iohexol concentration and trapezoidal area under the curve (tAUC). The iohexol-GFR significantly correlated with the Schwartz formula-eGFR. In macaques with renal irradiation doses below 6 Gy, GFR was higher for males than females. GFR was lower in macaques with renal irradiation doses greater than 6 Gy compared to macaques with renal doses less than 6 Gy. We conclude that use of the Schwartz formula can provide a rapid, non-invasive, cost-effective, and accurate estimation of GFR to aid in the clinical assessment of renal function in irradiated rhesus macaques.

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A method for estimating the glomerular filtration rate in conscious monkeys

Cited by 3 publications

References 21 publications

Comparative Pharmacokinetics of Puerarin Alone and in Pueraria mirifica Extract in Female Cynomolgus Monkeys

Comparative Pharmacokinetics of Puerarin Alone and in Pueraria mirifica Extract in Female Cynomolgus Monkeys

Comparative pharmacokinetics of puerarin in pure compound form and puerarin in white kwao krua extract in female cynomolgus monkeys

A New Method for Estimating Glomerular Filtration Rate in Rhesus Macaques (Macaca mulatta)

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