scholarly journals Population Pharmacokinetics Modeling of Levofloxacin In Rabbit By Intravenous Bolus Injection and Peroral Administration

2021 ◽  
Author(s):  
Akhmad Kharis Nugroho ◽  
Puspa Dwi Pratiwi ◽  
Shesanti Citrariana ◽  
Endang Lukitaningsih ◽  
Lukman Hakim
Keyword(s):  
Goodness Of Fit ◽  
Bolus Injection ◽  
Pharmacokinetic Profile ◽  
Population Based ◽  
Peroral Administration ◽  
Intravenous Bolus ◽  
Intravenous Bolus Injection ◽  
The Individual ◽  
Disposition Model ◽  
Parameter Values

The population-based approach has been widely applied to describe the pharmacokinetic profile of many drugs. The aim of this current research was to study the implementation of the population-based pharmacokinetics of levofloxacin in rabbits administered by intravenous bolus injection and peroral delivery. Modeling analyses were performed using Monolix, one of the alternative tools for the population-based approach. Monolix works based on the Stochastic Approximation Expectation-Maximization (SAEM) method. The analysis was performed based on the population model using one-compartmental and two-compartmental disposition models. The combination error model was used during the analyses. Modeling appropriateness was determined based on the goodness of fit analyses, i.e., 1) the individual fit, 2) the observed versus population prediction values; and 3) the observed versus individual prediction values Plasma concentration profiles of levofloxacin by intravenous bolus injection and oral administration are better described by an appropriate model using a two-compartmental disposition model. All goodness of fit analyses demonstrates the power of the chosen model. However, the estimated disposition parameter values obtained based on the intravenous bolus injection and peroral administration are different for each subject. To confirm this phenomenon, we performed a simultaneous fitting of all intravenous bolus as well as peroral administration data. The goodness of fit analyses indicates an adequate fitting of all data.

Pharmacological properties of YM-254890, a specific Gαq/11 inhibitor, on thrombosis and neointima formation in mice

2005 ◽  
Vol 94 (07) ◽  
pp. 184-192 ◽  
Author(s):  
Masatoshi Taniguchi ◽  
Yumiko Moritani ◽  
Toshio Uemura ◽  
Takeshi Shigenaga ◽  
Hajime Takamatsu ◽  
...  
Keyword(s):  
Oral Administration ◽  
Vascular Injury ◽  
Bolus Injection ◽  
Thrombus Formation ◽  
Therapeutic Window ◽  
Pharmacological Properties ◽  
Neointima Formation ◽  
Intravenous Bolus ◽  
Test Drug ◽  
Intravenous Bolus Injection

SummaryThe pharmacological properties of YM-254890,a specific Gαq/11 inhibitor, on acute thrombosis and chronic neointima formation after vascular injury have been investigated. FeCl3 was used to induce vascular injury in the carotid artery of mice. For the thrombosis studies, the test drug was either intravenously or orally administered before vascular injury. For the neointima studies, the test drug was orally administered 1 h before and twice daily for 1 week after vascular injury. Histological analysis was then performed 3 weeks later. YM-254890 significantly inhibited ex vivo platelet aggregation 5 min after intravenous bolus injection at 0.03 mg/kg or more, and 1 h after oral administration at 1 mg/kg. YM-254890 significantly inhibited thrombus formation after intravenous bolus injection at 0.03 mg/kg as well as after oral administration at 1 mg/kg, but tail transection bleeding time was significantly prolonged at 0.1 mg/kg for intravenous injection and 3 mg/kg for oral administration. Furthermore, oral administration of YM-254890 dose-dependently inhibited neointima formation 3 weeks after vascular injury with significant effects at 1 mg/kg twice daily for 1 week. Clopidogrel also significantly inhibited neointima formation at its antithrombotic dose, but its inhibitory potency was less than that of YM-254890. However, YM-254890 significantly reduced systemic blood pressure at doses 3 times higher than those that produced significant inhibitory effects on thrombosis and neointima formation. Though the systemic use of YM-254890 may be limited, owing to its narrow therapeutic window, this unique compound is a useful research tool for investigating the physiological roles of Gαq/11.

In Vivo Utilization of Cystine-Containing Synthetic Short-Chain Peptides after Intravenous Bolus Injection in the Rat

1988 ◽  
Vol 118 (12) ◽  
pp. 1470-1474 ◽  
Author(s):  
Peter Stehle ◽  
Sabine Albers ◽  
Leonhard Pollack ◽  
Peter Fürst
Keyword(s):  
Bolus Injection ◽  
Short Chain ◽  
Intravenous Bolus ◽  
Intravenous Bolus Injection

Effects of glucagon, insulin, propionate, acetate, and HCO3 on K excretion in sheep

1984 ◽  
Vol 246 (2) ◽  
pp. R197-R204
Author(s):  
L. Rabinowitz ◽  
R. L. Sarason ◽  
C. Tanasovich ◽  
V. E. Mendel ◽  
R. P. Brockman
Keyword(s):  
Intravenous Infusion ◽  
Bolus Injection ◽  
Urine Flow ◽  
Intravenous Bolus ◽  
Treatment Control ◽  
Hormone Levels ◽  
Intravenous Bolus Injection ◽  
Fasted State ◽  
Glucagon And Insulin

The effects on renal K excretion of 1 h intravenous infusion of glucagon, insulin, Na propionate, Na acetate, or NaHCO3 were studied in mature, conscious fasted ewes. These treatments were compared with the fasted state without treatment (control) and with feeding a single daily meal. Renal K excretion was increased by feeding and by Na propionate and Na acetate treatments but not by infusion of glucagon, insulin, and NaHCO3. Since hormone levels were elevated more by specific hormone infusions than by feeding or Na propionate infusions, these results do not support a role for glucagon and insulin in mediating the increases in renal K excretion that occurred after meals or during acetate and propionate infusions. The mechanisms responsible for the acetate- and propionate-induced kaliuresis are not clear but do not appear to include changes in plasma K (PK), glucagon, and insulin (Pinsulin) or in urine flow and urine Na excretion. However, a relation between insulin and K was observed during infusion of KCl in fasting sheep. Above a PK threshold of 4 meq/l, Pinsulin (ng/ml) = 1.52 PK (meq/l) - 5.89. In other experiments, K excretion increased after an intravenous bolus injection of 1 mg of glucagon, indicating that sheep, like humans and dogs, respond to pharmacologic doses of glucagon with kaliuresis.

Single Dose Pharmacokinetics of a Recombinant FVIIa In Factor VIII KO Mice, Rats, and Cynomolgus Monkeys

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4655-4655
Author(s):  
Gerald Hoebarth ◽  
Susan Kubik ◽  
Martin Wolfsegger ◽  
John-Philip Lawo ◽  
Alfred Weber ◽  
...  
Keyword(s):  
Single Dose ◽  
Bolus Injection ◽  
Intravenous Bolus ◽  
Plasma Samples ◽  
Total Clearance ◽  
Cynomolgus Monkeys ◽  
Intravenous Bolus Injection ◽  
Terminal Half Life ◽  
Secondary Endpoints ◽  
Time Point

Abstract Abstract 4655 The purpose of these PK studies was to assess the pharmacokinetic profile of Baxter's rFVIIa in comparison with a commercially available rFVIIa after a single intravenous bolus injection at a target dose of 0.6 mg/kg BW in mice and rats and 2.7 mg/kg BW in cynomolgus monkeys. The AUC0-t last (the area under the concentration vs. time curve from 0 to the last measured time point) was evaluated as primary endpoint. Secondary endpoints were terminal half-life (HL), mean residence time (MRT) and total clearance standardized per kg body mass (Cl) for FVIIa protein and clotting activity. In cynomolgus monkeys only FVIIa clotting activity was evaluated. Blood was sampled at baseline and each of the time points after a single intravenous bolus injection of Baxter's rFVIIa or the commercially available rFVIIa. The citrated plasma samples were analyzed for FVIIa activity and FVII protein (antigen). A serial sacrifice design was used for the PK in mice. Ten FVIII ko mice (B6;129S4-F8tm1Kaz; 5m/5f) per time point were bled by cardiac puncture under anesthesia for blood sampling 5 – 200 minutes after a single intravenous bolus injection. A single animals design was used for the single dose PK in Sprague Dawley rats (5m/5f) and cynomolgus monkeys (2m/2f). In rats and cynomolgus monkeys blood samples for citrated plasma were drawn before administration (for analysis of baseline FVIIa levels) and 5 – 270 minutes (rats) or 5 minutes to 15 hours (cynomolgus monkeys) after administration. Plasma samples were analyzed for FVIIa protein (antigen) using a FVII ELISA calibrated for FVIIa measurement and for FVIIa activity using a FVIIa clotting assay. In all three species bioequivalence of Baxter's rFVIIa and the reference item could be shown for the primary endpoint (AUC0-tlast) for FVIIa activity and antigen (the latter was only tested in mice and rats). Additionally, secondary endpoints of FVIIa activity (terminal half-life, mean residence time and total clearance) were similar for Baxter's rFVIIa and the reference item. In mice, HL was 0.64 h, MRT was 0.80 h and Cl was 245 ml/kg/h for Baxter's new rFVIIa. Values for the secondary endpoints in rats were 1.17 h for HL, 1.29 h for MRT and 102.6 mL/kg/h for Cl. In cynomolgus monkeys, HL was 2.00 h, MRT was 2.45 h and Cl was 33.6 mL/kg/h. In summary, the pharmacokinetic profiles of Baxter's rFVIIa and the commercially available rFVIIa were similar in all species studied. Disclosures: Hoebarth: Baxter Innovations GmbH: Employment. Kubik:Baxter Innovations GmbH: Employment. Wolfsegger:Baxter Innovations GmbH: Employment. Lawo:Baxter Innovations GmbH: Employment. Weber:Baxter Innovations GmbH: Employment. Gritsch:Baxter Innovations GmbH: Employment. Ehrlich:Baxter Innovations GmbH: Employment. Scheiflinger:Baxter Innovations GmbH: Employment. Schwarz:Baxter Innovations GmbH: Employment. Muchitsch:Baxter Innovations GmbH: Employment.

Phase I Clinical Trial of Lobaplatin (D-19466) after Intravenous Bolus Injection

1994 ◽  
Vol 17 (2) ◽  
pp. 142-148 ◽  
Author(s):  
H.H. Fiebig ◽  
H. Henß ◽  
K. Mross ◽  
F. Meyberg ◽  
P. Aulenbacher ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Bolus Injection ◽  
Phase I Clinical Trial ◽  
Intravenous Bolus ◽  
Intravenous Bolus Injection
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