Göttingen
2021年4月19日Register here: http://gg.gg/p3esz
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*Search the world’s information, including webpages, images, videos and more. Google has many special features to help you find exactly what you’re looking for.
*Real-time meetings by Google. Using your browser, share your video, desktop, and presentations with teammates and customers.Liraglutide Pharmacokinetic Profile Following SC Dosing Is Unaltered by Co-Administration with Sitagliptin in Göttingen Minipigs Liraglutide is a once-daily h Liraglutide is a once-daily human Glucagon-Like Peptide-1 (GLP-1) analog that has completed phase 3 clinical testing. Liraglutide is a fatty-acid derived analog of human GLP-1 that binds to albumin as its main mechanism of protraction. Liraglutide is also stabilized against the DPP-IV enzyme. However, liraglutide is subject to a minor degradation in vivo, and thus it is interesting if co-administration with a DPP-IV inhibitor lead to increases in liraglutide concentrations. Sitagliptin is a DPP-IV inhibitor that increases endogenous levels of GLP-1, which is the main mechanism for its blood glucose lowering ability. Since both compounds lead to increases in GLP-1-like concentrations (either liraglutide or native GLP-1), we investigated if they could be combined by investigating the pharmacokinetics of liraglutide following co-administration of liraglutide and sitagliptin. The study was carried out in minipigs because only pigs have a similar absorption of injectable peptide analogs as compared to humans. Sitagliptin is dosed once daily PO (100 mg) in patients, resulting in a steady state trough plasma concentration of 41 ng/mL. Liraglutide is dosed once-daily SC (1.2 or 1.8 mg). The study was conducted in two parallel groups (+/- sitagliptin) of mini-pigs (n=4). Both groups were dosed SC with liraglutide in a dose of 2 nmol/kg, equivalent to app. 0.6 mg pr 75 kg. The sitagliptin group was dosed three times daily in order to obtain a target steady state trough plasma concentration of sitagliptin above 40 ng/mL. The key pharmacokinetic parameters (mean ±SD) of liraglutide are given in Table 1. Sitagliptin had no significant effect on the pharmacokinetics of liraglutide as evaluated by Tmax, Cmax, AUC/Dose and half-life. The mean plasma concentration of sitagliptin was verified to be above 40 ng/mL. In conclusion, the DPPIV inhibitor sitagliptin did not alter the pharmacokinetics of liraglutide following SC administration in mini-pigs.Table 1TreatmentTmax [hr]Cmax [pM]AUC/Dose [hr•pM/pmol/kg]T½ [hr]- Sitagliptin8.5 ±2.518000 ±3700278 ±3222 ±2.6+ Sitagliptin8.0 ±2.819600 ±2300322 ±5320 ±1.4p-value (t-test)0.800.520.210.20 FLEMMING SEIER NIELSEN, LARS YNDDAL, CHRISTIAN ROSENQUIST, JØRN DRUSTRUP, LOTTE BJERRE KNUDSEN 2065-PO Maaloev, Denmark Clinical Therapeutics/New Technology - Pharmacologic Treatment of Diabetes or its ComplicationsG DriveGmailClinical Therapeutics/New Technology - Pharmacologic Treatment of Diabetes or its Complications
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G-Code Q’n’dirty toolpath simulator. Paste your g-code in the left-hand window or drop a file on the page and see the preview of your tool path on the right. The right-hand pane are interactive, drag them to change the point of view.
*Search the world’s information, including webpages, images, videos and more. Google has many special features to help you find exactly what you’re looking for.
*Real-time meetings by Google. Using your browser, share your video, desktop, and presentations with teammates and customers.Liraglutide Pharmacokinetic Profile Following SC Dosing Is Unaltered by Co-Administration with Sitagliptin in Göttingen Minipigs Liraglutide is a once-daily h Liraglutide is a once-daily human Glucagon-Like Peptide-1 (GLP-1) analog that has completed phase 3 clinical testing. Liraglutide is a fatty-acid derived analog of human GLP-1 that binds to albumin as its main mechanism of protraction. Liraglutide is also stabilized against the DPP-IV enzyme. However, liraglutide is subject to a minor degradation in vivo, and thus it is interesting if co-administration with a DPP-IV inhibitor lead to increases in liraglutide concentrations. Sitagliptin is a DPP-IV inhibitor that increases endogenous levels of GLP-1, which is the main mechanism for its blood glucose lowering ability. Since both compounds lead to increases in GLP-1-like concentrations (either liraglutide or native GLP-1), we investigated if they could be combined by investigating the pharmacokinetics of liraglutide following co-administration of liraglutide and sitagliptin. The study was carried out in minipigs because only pigs have a similar absorption of injectable peptide analogs as compared to humans. Sitagliptin is dosed once daily PO (100 mg) in patients, resulting in a steady state trough plasma concentration of 41 ng/mL. Liraglutide is dosed once-daily SC (1.2 or 1.8 mg). The study was conducted in two parallel groups (+/- sitagliptin) of mini-pigs (n=4). Both groups were dosed SC with liraglutide in a dose of 2 nmol/kg, equivalent to app. 0.6 mg pr 75 kg. The sitagliptin group was dosed three times daily in order to obtain a target steady state trough plasma concentration of sitagliptin above 40 ng/mL. The key pharmacokinetic parameters (mean ±SD) of liraglutide are given in Table 1. Sitagliptin had no significant effect on the pharmacokinetics of liraglutide as evaluated by Tmax, Cmax, AUC/Dose and half-life. The mean plasma concentration of sitagliptin was verified to be above 40 ng/mL. In conclusion, the DPPIV inhibitor sitagliptin did not alter the pharmacokinetics of liraglutide following SC administration in mini-pigs.Table 1TreatmentTmax [hr]Cmax [pM]AUC/Dose [hr•pM/pmol/kg]T½ [hr]- Sitagliptin8.5 ±2.518000 ±3700278 ±3222 ±2.6+ Sitagliptin8.0 ±2.819600 ±2300322 ±5320 ±1.4p-value (t-test)0.800.520.210.20 FLEMMING SEIER NIELSEN, LARS YNDDAL, CHRISTIAN ROSENQUIST, JØRN DRUSTRUP, LOTTE BJERRE KNUDSEN 2065-PO Maaloev, Denmark Clinical Therapeutics/New Technology - Pharmacologic Treatment of Diabetes or its ComplicationsG DriveGmailClinical Therapeutics/New Technology - Pharmacologic Treatment of Diabetes or its Complications
Register here: http://gg.gg/p3esz
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