Pharmacokinetics of Recombinant Human Endostatin in Rats

Yang, Xiao; Hu, Zen Ping; Chan, Eli; Duan, Wei; Zhou, Shu‐Feng

doi:10.2174/138920006778017803

Cited by 11 publications

(6 citation statements)

References 81 publications

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“…Furthermore, it is necessary to consider the influence of renal clearance of circulating endostatin as well as the endostatin-producing increase. Urinary excretion was the major elimination route of endostatin in an animal experiment 31 ) . Elevation of serum endostatin level may be due to decreased renal clearance, similar to that of cystatin C. Both cystatin C and endostatin are of similar size and can pass through the glomerular barrier 12 ) .…”

Section: Discussionmentioning

confidence: 98%

Association of the Serum Endostatin Level, Renal Function, and Carotid Atherosclerosis of Healthy Residents of Japan: Results from the Kyushu and Okinawa Population Study (KOPS)

Kato

Furusyo

Tanaka

et al. 2018

J Atheroscler Thromb

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Aim: To analyze associations among the serum endostatin level, renal function, and carotid atherosclerosis of healthy residents of Japan.Methods: Among 1,057 Japanese residents who attended free public physical examinations between 2010 and 2011, we evaluated the data of 648 healthy residents (200 men and 448 women, age 24 to 84 years) for whom the serum endostatin level and common carotid intima-media thickness (IMT) were measured. Renal function was assessed by estimated glomerular filtration rate (eGFR). Multiple linear regression analysis was done to determine the association of eGFR and serum endostatin level after adjustment for known covariates. Mediation analysis was done using Baron and Kenny's regression approach.Results: The median endostatin level was 63.7 ng/mL (interquartile range: 49.7–93.2). The mean eGFR was 78.4 ± 14.8 mL/min/1.73m2. Univariate analysis showed that age (r = −0.37, P < 0.01), non current smoking (85.8 ± 13.0 vs. 77.5 ± 14.8 mL/min/1.73 m2, P < 0.01), hemoglobin A1c (r = −0.08, P = 0.05), low-density lipoprotein-cholesterol (r = −0.13, P < 0.01), uric acid (r = −0.15, P < 0.01), carotid IMT (r = −0.11, P < 0.01), and log-transformed endostatin (r = −0.36, P < 0.01) were significantly associated with eGFR. In multiple linear regression analysis, log-transformed endostatin was significantly associated with eGFR (beta = −0.24, P < 0.01). While, carotid IMT was no longer significant. Mediation analysis showed serum endostatin level to be a mediator in the association between carotid IMT and eGFR.Conclusions: The association between carotid IMT and eGFR is mediated by the serum endostatin level of healthy individuals.

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Section: Discussionmentioning

confidence: 98%

Association of the Serum Endostatin Level, Renal Function, and Carotid Atherosclerosis of Healthy Residents of Japan: Results from the Kyushu and Okinawa Population Study (KOPS)

Kato

Furusyo

Tanaka

et al. 2018

J Atheroscler Thromb

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“…In previous studies, the pharmacokinetics of rhendostatin were reported in rats and rhesus monkeys [30,31] .…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of PEGylated recombinant human endostatin (M2ES) in rats

Zuo-gang¹,

Jia²,

Guo

et al. 2015

Acta Pharmacol Sin

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Aim: M 2 ES is PEGylated recombinant human endostatin. In this study we investigated the pharmacokinetics, tissue distribution, and excretion of M 2 ES in rats. Methods: 125 I-radiolabeled M 2 ES was administered to rats by intravenous bolus injection at 3 mg/kg. The pharmacokinetics, tissue distribution and excretion of M 2 ES were investigated using the trichloroacetic acid (TCA) precipitation method. Results: The serum M 2 ES concentration-time curve after a single intravenous dose of 3 mg/kg in rats was fitted with a noncompartment model. The pharmacokinetic parameters were evaluated as follows: C max =28.3 μg·equ/mL, t 1/2 =71.5 h, AUC (0-∞) =174.6 μg·equ·h/mL, Cl=17.2 mL·h -1 ·kg -1 , MRT=57.6 h, and V ss =989.8 mL/kg for the total radioactivity; C max =30.3 μg·equ/mL, t 1/2 =60.1 h, AUC (0-∞) =146.2 μg·equ·h/mL, Cl=20.6 mL·h -1 ·kg -1 , MRT=47.4 h, and V ss =974.6 mL/kg for the TCA precipitate radioactivity. M 2 ES was rapidly and widely distributed in various tissues and showed substantial deposition in kidney, adrenal gland, lung, spleen, bladder and liver. The radioactivity recovered in the urine and feces by 432 h post-dose was 71.3% and 8.3%, respectively. Only 0.98% of radioactivity was excreted in the bile by 24 h post-dose. Conclusion: PEG modification substantially prolongs the circulation time of recombinant human endostatin and effectively improves its pharmacokinetic behavior. M 2 ES is extensively distributed in most tissues of rats, including kidney, adrenal gland, lung, spleen, bladder and liver. Urinary excretion was the major elimination route for M 2 ES.

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“…The high levels may in HD patients may additionally be explained by the fact that urinary excretion is the major elimination route of endostatin [34].…”

Section: Discussionmentioning

confidence: 99%