scholarly journals Pharmacokinetic Comparison of Three Different Administration Routes for Topotecan Hydrochloride in Rats

2020 ◽  
Vol 13 (9) ◽  
pp. 231
Author(s):  
Seung-Hyun Jeong ◽  
Ji-Hun Jang ◽  
Yong-Bok Lee
Keyword(s):  
Oral Administration ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Elimination Phase ◽  
Routes Of Administration ◽  
Administration Routes ◽  
Pharmacokinetic Profiles

Topotecan is actively used in clinic, with its primary use being in treatment of various types of cancer. The approved administration routes are oral and intravenous. The purpose of this study was to investigate and identify pharmacokinetic profiles of different administration routes. We conducted pharmacokinetic studies on three different routes of administration in rats. Five rats in each group received a single dose of 4 mg/kg of topotecan hydrochloride intravenously, orally, or subcutaneously, and the concentrations of lactone and total forms of the drug in plasma, urine, and feces were quantified. Various pharmacokinetic parameters were compared statistically. Plasma concentrations of both the lactone and total forms at elimination phase following subcutaneous administration, were two times higher than was seen with oral administration and 10 times higher than with intravenous administration. Subcutaneous administration of topotecan showed pharmacokinetic profiles similar to sustained release. In addition, subcutaneous administration showed bioavailability from 88.05% (for lactone form) to 99.75% (for total form), and these values were four–five times greater than those of oral administration. The results of this non-clinical study will not only provide greater understanding of the in vivo pharmacokinetics of topotecan, but also be useful for development of additional formulations and/or administration routes.

scholarly journals Toxicity and Pharmacokinetic Studies of Lidocaine and Its Active Metabolite, Monoethylglycinexylidide, in Goat Kids

Animals ◽  
2018 ◽  
Vol 8 (8) ◽  
pp. 142
Author(s):  
Dinakaran Venkatachalam ◽  
Paul Chambers ◽  
Kavitha Kongara ◽  
Preet Singh
Keyword(s):  
Total Dose ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Lidocaine Hydrochloride ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Liquid Chromatography Mass Spectrometry ◽  
Elimination Half ◽  
The Mean ◽  
Safe Dose

This study determined the convulsant plasma concentrations and pharmacokinetic parameters following cornual nerve block and compared the results to recommend a safe dose of lidocaine hydrochloride for goat kids. The plasma concentrations of lidocaine and monoethylglycinexylidide (MGX) were quantified using liquid chromatography-mass spectrometry. A total dose of 7 mg/kg body weight (BW) was tolerated and should therefore be safe for local and regional anesthesia in goat kids. The mean plasma concentration and mean total dose that produced convulsions in goat kids were 13.59 ± 2.34 µg/mL and 12.31 ± 1.42 mg/kg BW (mean ± S.D.), respectively. The absorption of lidocaine following subcutaneous administration was rapid with Cmax and Tmax of 2.12 ± 0.81 µg/mL and 0.33 ± 0.11 h, respectively. The elimination half-lives (t½λz) of lidocaine hydrochloride and MGX were 1.71 ± 0.51 h and 3.19 ± 1.21 h, respectively. Injection of 1% lidocaine hydrochloride (0.5 mL/site) was safe and effective in blocking the nerves supplying horn buds in goat kids.

scholarly journals Pharmacokinetic Profile of μSMIN Plus™, a new Micronized Diosmin Formulation, after Oral Administration in Rats

2015 ◽  
Vol 10 (9) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Rosario Russo ◽  
Angelo Mancinelli ◽  
Michele Ciccone ◽  
Fabio Terruzzi ◽  
Claudio Pisano ◽  
...  
Keyword(s):  
Oral Administration ◽  
Plasma Concentrations ◽  
Compartmental Analysis ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Sprague Dawley ◽  
Time Curve ◽  
Maximum Plasma Drug Concentration

Diosmin is a naturally occurring flavonoid present in citrus fruits and other plants belonging to the Rutaceae family. It is used for the treatment of chronic venous insufficiency (CVI) for its pheblotonic and vaso-active properties, safety and tolerability as well. The aim of the current in vivo study was to investigate the pharmacokinetic profile of a branded micronized diosmin (μSMIN Plus™) compared with plain micronized diosmin in male Sprague-Dawley rats. After oral administration by gastric gavage, blood samples were collected via jugular vein catheters at regular time intervals from baseline up to 24 hours. Plasma concentrations were assessed by LC/MS. For each animal, the following pharmacokinetic parameters were calculated using a non-compartmental analysis: maximum plasma drug concentration (Cmax), time to reach Cmax (Tmax), area under the plasma concentration-time curve (AUC0-last), elimination half-life (t1/2), and relative oral bioavailability (%F). The results of the current study clearly showed an improvement in the pharmacokinetic parameters in animals treated with μSMIN Plus™ compared with animals treated with micronized diosmin. In particular, μSMIN Plus™ showed a 4-fold increased bioavailability compared with micronized diosmin. In conclusion, the results from the current study provided a preliminary pharmacokinetic profile for μSMIN Plus™, which may represent a new tool for CVI management.

scholarly journals Pharmacokinetic Comparison of 20(R)- and 20(S)-Ginsenoside Rh1 and 20(R)- and 20(S)-Ginsenoside Rg3 in Rat Plasma following Oral Administration of Radix Ginseng Rubra and Sheng-Mai-San Extracts

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaomei Fan ◽  
Yan Xu ◽  
Danni Zhu ◽  
Yibing Ji
Keyword(s):  
Oral Administration ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Spectrometric Method ◽  
Pharmacokinetic Studies ◽  
Mass Spectrometric Method ◽  
Ginsenoside Rg3 ◽  
Radix Ginseng

Ginsenosides Rh1 and Rg3, as the main bioactive components from Ginseng, are effective for prevention and treatment of cardiovascular diseases. Sheng-Mai-San (SMS), a classical complex prescription of traditional Chinese medicines, is composed of Radix Ginseng Rubra, Fructus Schisandrae, and Radix Ophiopogonis. In this research, a sensitive and specific liquid chromatography-mass spectrometric method was developed and validated for stereoselective determination and pharmacokinetic studies of 20(R)- and 20(S)-ginsenoside Rh1 and 20(R)- and 20(S)-ginsenoside Rg3 epimers in rat plasma after oral administration of Radix Ginseng Rubra or SMS extracts. The main pharmacokinetic parameters including Tmax, Cmax, t1/2, and AUC were calculated by noncompartment model. Compared with Radix Ginseng Rubra, SMS could significantly increase the content of ginsenosides Rh1 and Rg3 in the decocting process. Ginsenosides Rh1 and Rg3 following SMS treatment displayed higher Cmax, AUC(0–t), and AUC0–∞ and longer t1/2 and tmax except for 20(R)-Rh1 in rat plasma. The results indicated SMS compound compatibility could influence the dissolution in vitro and the pharmacokinetic behaviors in vivo of ginsenosides Rh1 and Rg3, suggesting pharmacokinetic drug-drug interactions between ginsenosides Rh1 and Rg3 and other ingredients from Fructus Schisandrae and Radix Ophiopogonis. This study would provide valuable information for drug development and clinical application of SMS.

Rapid evaluation of rumen protection status of orally administered DL-methionine mixes using an HPLC analysis of plasma methionine

1991 ◽  
Vol 31 (3) ◽  
pp. 315 ◽  
Author(s):  
RGA Stephenson ◽  
L PalmerC ◽  
GR Suter
Keyword(s):  
Oral Administration ◽  
Protein Hydrolysate ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Positive Control ◽  
Bacterial Degradation ◽  
Laboratory Evaluation ◽  
Wool Growth ◽  
Head Level

The measurement of plasma methionine concentrations with high pressure liquid chromatography (HPLC) with a protein hydrolysate column was examined as a means of evaluating the rumen protection status of DL-methionine mixes after oral administration. Plasma methionine concentrations were measured 2, 4, 6 and 8 h after 5 different mixes had been administered to the rumen of 3 sheep by stomach tube. The plasma values were compared with the pretreatment profile (1.2-16.7 �mol/L) obtained in the test sheep, and those obtained after abomasal and subcutaneous administration. The results suggest that none of the mixes were significantly protected from bacterial degradation in the rumen. The positive control treatments of subcutaneous or abomasal administration resulted in >10-fold increases in plasma concentrations of methionine (e.g. from 28 to 414 �mol/L). A method of administration that required the sheep to raise their heads about 30 cm to lick a molasses + methionine mix increased subsequent plasma methionine concentrations 5 times (from 44 to 267 �mol/L). Oral administration of 2 mixes using a drench gun also resulted in increased plasma methionine in some sheep, suggesting that these procedures allowed some methionine to bypass the rumen mechanically. A follow-on wool growth experiment using methionine + molasses mixes administered either from a 'licker' 30 cm above head level or in the feedbin failed to increase either wool growth or plasma methionine. The HPLC procedure for methionine analysis proved successful for the qualitative laboratory evaluation of the rumen protection status of methionine mixes. It is concluded that this 24 h methionine test and analysis procedure can partly replace the costly and lengthy in vivo procedure of measuring responses in wool production.

scholarly journals Identification and Pharmacokinetic Studies on Complanatuside and Its Major Metabolites in Rats by UHPLC-Q-TOF-MS/MS and LC-MS/MS

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 71 ◽  
Author(s):  
Yu-Feng Yao ◽  
Chao-Zhan Lin ◽  
Fang-Le Liu ◽  
Run-Jing Zhang ◽  
Qiu-Yu Zhang ◽  
...  
Keyword(s):  
Oral Administration ◽  
Degradation Products ◽  
Plasma Concentrations ◽  
Rat Plasma ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Studies ◽  
Maximum Plasma ◽  
Time Curve ◽  
Tof Ms

The metabolic and pharmacokinetic studies on complanatuside, a quality marker of a Chinese materia medicatonic, Semen Astragali Complanati, were carried out. The UHPLC-Q-TOF/MS (ultra-high performance liquid chromatography coupled with electrospray ionization tandem quadrupole-time-of-flight mass spectrometry) method was applied to identify the metabolites of complanatuside in rat plasma, bile, stool, and urine after oral administration at the dosage of 72 mg/kg. Up to 34 metabolites (parent, 2 metabolites of the parent drug, and 31 metabolites of the degradation products) were observed, including processes of demethylation, hydroxylation, glucuronidation, sulfonation, and dehydration. The results indicated glucuronidation and sulfonation as major metabolic pathways of complanatuside in vivo. Meanwhile, a HPLC-MS method to quantify complanatuside and its two major metabolites—rhamnocitrin 3-O-β-glc and rhamnocitrin—in rat plasma for the pharmacokinetic analysis was developed and validated. The Tmax (time to reach the maximum drug concentration) of the above three compounds were 1 h, 3 h, and 5.3 h, respectively, while the Cmax (maximum plasma concentrations)were 119.15 ng/mL, 111.64 ng/mL, and 1122.18 ng/mL, and AUC(0-t) (area under the plasma concentration-time curve) was 143.52 µg/L·h, 381.73 µg/L·h, and 6540.14 µg/L·h, accordingly. The pharmacokinetic characteristics of complanatuside and its two metabolites suggested that complanatuside rapidly metabolized in vivo, while its metabolites—rhamnocitrin—was the main existent form in rat plasma after oral administration. The results of intracorporal processes, existing forms, and pharmacokinetic characteristics of complanatuside in rats supported its low bioavailability.

scholarly journals Pharmacological Properties of a New Antimalarial Bisthiazolium Salt, T3, and a Corresponding Prodrug, TE3

2005 ◽  
Vol 49 (9) ◽  
pp. 3631-3639 ◽  
Author(s):  
Olivier Nicolas ◽  
Delphine Margout ◽  
Nicolas Taudon ◽  
Sharon Wein ◽  
Michèle Calas ◽  
...  
Keyword(s):  
Oral Administration ◽  
Antimalarial Activity ◽  
Plasma Concentrations ◽  
Intraperitoneal Administration ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Pharmacological Properties ◽  
Mean Values

ABSTRACT A new approach to malarial chemotherapy based on quaternary ammonium that targets membrane biogenesis during intraerythrocytic Plasmodium falciparum development has recently been developed. To increase the bioavailability, nonionic chemically modified prodrugs were synthesized. In this paper, the pharmacological properties of a bisthiazolium salt (T3) and its bioprecursor (TE3) were studied. Their antimalarial activities were determined in vitro against the growth of P. falciparum and in vivo against the growth of P. vinckei in mice. Pharmacokinetic evaluations were performed after T3 (1.3 and 3 mg/kg of body weight administered intravenously; 6.4 mg/kg administered intraperitoneally) and TE3 (1.5 and 3 mg/kg administered intravenously; 12 mg/kg administered orally) administrations to rats. After intraperitoneal administration, very low doses offer protection in a murine model of malaria (50% efficient dose [ED50] of 0.2 to 0.25 mg/kg). After oral administration, the ED50 values were 13 and 5 mg/kg for T3 and TE3, respectively. Both compounds exerted antimalarial activity in the low nanomolar range. After TE3 administration, rapid prodrug-drug conversion occurred; the mean values of the pharmacokinetic parameters for T3 were as follows: total clearance, 1 liter/h/kg; steady-state volume of distribution, 14.8 liters/kg; and elimination half-life, 12 h. After intravenous administration, T3 plasma concentrations increased in proportion to the dose. The absolute bioavailability was 72% after intraperitoneal administration (T3); it was 15% after oral administration (TE3). T3 plasma concentrations (8 nM) 24 h following oral administration of TE3 were higher than the 50% inhibitory concentrations for the most chloroquine-resistant strains of P. falciparum (6.3 nM).

scholarly journals Pharmacokinetics of Luteolin and Metabolites in Rats

2008 ◽  
Vol 3 (12) ◽  
pp. 1934578X0800301 ◽  
Author(s):  
Sasiporn Sarawek ◽  
Hartmut Derendorf ◽  
Veronika Butterweck
Keyword(s):  
Oral Administration ◽  
Intravenous Administration ◽  
Plasma Concentrations ◽  
Maximum Level ◽  
Volume Of Distribution ◽  
Time Profile ◽  
Oral Solution ◽  
Pharmacokinetic Parameters ◽  
Elimination Phase ◽  
Intravenous And Oral Administration

The pharmacokinetic parameters of luteolin and its glucuronide/sulfate conjugates were studied in rats after a single 50 mg/kg dose of luteolin administered as intravenous bolus or oral solution. Plasma and urine samples were enzymatically hydrolyzed to determine conjugate concentrations of luteolin. Noncompartmental analysis revealed a half-life of 8.94 h for free (unconjugated) and 4.98 h for conjugated luteolin following intravenous administration. Following oral administration, plasma concentrations of luteolin attained a maximum level of 5.5 μg/mL at 5 min and decreased to below LOQ (100 ng/mL) after 1 h. Ke could not be calculated because the elimination phase was below LOQ. The low bioavailability (F) of luteolin, 4.10% at a dose of 50 mg/kg, is presumably due to the significant first pass effect. For i.v. administration, the maximum concentration of luteolin was 23.4 μg/mL at 0 h. The plasma concentration versus time profile of luteolin was biphasic, subdivided into a distribution phase and a slow elimination phase for oral and intravenous administration. Luteolin was found to have a large volume of distribution and a high clearance. Double peaks were found after intravenous and oral administration, suggesting enterohepatic recirculation.

A Multicenter Study of Recombinant Factor VIII (RecombinateTM) in Previously Treated Patients with Hemophilia A

1997 ◽  
Vol 77 (04) ◽  
pp. 660-667 ◽  
Author(s):  
G C White ◽  
S Courter ◽  
G L Bray ◽  
M Lee ◽  
E D Gomperts ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Recombinant Dna ◽  
Home Treatment ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Open Label ◽  
Treat Ment ◽  
Previously Treated Patients ◽  
Bleeding Episodes

SummaryA prospective, open-label multicenter investigation has been conducted to compare pharmacokinetic parameters of recombinant DNA-derived FVIII (rFVIII) and plasma-derived FVIII concentrate (pdFVIII) and to assess safety and efficacy of long-term home-treat- ment with rFVIII for subjects with hemophilia A. Following comparative in vivo pharmacokinetic studies, 69 patients with severe (n = 67) or moderate (n = 2) hemophilia A commenced a program of home treatment using rFVIII exclusively for prophylaxis and treatment of all bleeding episodes for a period of 1.0 to 5.7 years (median 3.7 years). The mean in vivo half-lives of rFVIII and pdFVIII were both 14.7 h. In vivo incremental recoveries at baseline were 2.40%/IU/kg and 2.47%/IU/kg, respectively (p = 0.59). The response to home treatment with rFVIII was categorized as good or excellent in 3,195 (91.2%) of 3,481 evaluated bleeding episodes. Thirteen patients received rFVIII for prophylaxis for twenty-four surgical procedures. In all cases, hemostasis was excellent. Adverse reactions were observed in only 13 of 13,591 (0.096%) infusions of rFVIII; none was serious. No patient developed an inhibitor to r FVIII.

scholarly journals Biodistribution of Mesenchymal Stromal Cells after Administration in Animal Models and Humans: A Systematic Review

2021 ◽  
Vol 10 (13) ◽  
pp. 2925
Author(s):  
Manuel Sanchez-Diaz ◽  
Maria I. Quiñones-Vico ◽  
Raquel Sanabria de la Torre ◽  
Trinidad Montero-Vílchez ◽  
Alvaro Sierra-Sánchez ◽  
...  
Keyword(s):  
Animal Models ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cellular Therapy ◽  
The Body ◽  
Intralesional Injection ◽  
Intraarterial Infusion ◽  
Routes Of Administration ◽  
Administration Routes

Mesenchymal Stromal Cells (MSCs) are of great interest in cellular therapy. Different routes of administration of MSCs have been described both in pre-clinical and clinical reports. Knowledge about the fate of the administered cells is critical for developing MSC-based therapies. The aim of this review is to describe how MSCs are distributed after injection, using different administration routes in animal models and humans. A literature search was performed in order to consider how MSCs distribute after intravenous, intraarterial, intramuscular, intraarticular and intralesional injection into both animal models and humans. Studies addressing the biodistribution of MSCs in “in vivo” animal models and humans were included. After the search, 109 articles were included in the review. Intravenous administration of MSCs is widely used; it leads to an initial accumulation of cells in the lungs with later redistribution to the liver, spleen and kidneys. Intraarterial infusion bypasses the lungs, so MSCs distribute widely throughout the rest of the body. Intramuscular, intraarticular and intradermal administration lack systemic biodistribution. Injection into various specific organs is also described. Biodistribution of MSCs in animal models and humans appears to be similar and depends on the route of administration. More studies with standardized protocols of MSC administration could be useful in order to make results homogeneous and more comparable.

scholarly journals Plasma and tissue clindamycin antimicrobial activity after parenteral administration to cats under surgical conditions

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Sabrina Passini ◽  
Laura Montoya ◽  
Martín Lupi ◽  
Paula Lorenzini ◽  
María Fabiana Landoni ◽  
...  
Keyword(s):  
Peak Plasma ◽  
Subcutaneous Tissue ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Dose Interval ◽  
Tissue Concentrations ◽  
Administration Routes ◽  
Infection Treatment ◽  
Plasma Concentration Ratio ◽  
Surgical Conditions

Clindamycin plasma and tissue disposition in cats under surgical conditions after a single intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration at a dose rate of 10 mg/kg were studied. After intravenous, intramuscular and subcutaneous administration, peak plasma concentrations were 10.93±3.78 μg/mL (Cp(0)), 5.93±1.18 μg/mL (Cmax)) and 6.30±0.88 μg/mL (Cmax)), respectively. Eight hours after clindamycin IV, IM and SC administration plasma concentrations declined to 2.01±0.61 μg/mL, 2.96±0.43 μg/mL and 3.36±0.97 μg/mL, respectively. Sixty to 90 minutes after clindamycin administration, tissue concentrations ranged from a minimum in subcutaneous tissue of 4.90 μg/g (IV), 3.06 μg/g (IM) and, 3.13 μg/g (SC) to a maximum in uterus of 13.41 μg/g (IV), 14.07 μg/g (IM) and, 14.44 μg/g (SC). The lowest tissue/plasma concentration ratio for the three administration routes was observed in subcutaneous tissue, while the highest was observed at genital level (ovary for IV and IM and uterus for SC). Estimated efficacy predictor (AUC/MIC), considering MIC breakpoint for bacteria isolated from animals, indicates that clindamycin administered IV, IM or SC at the studied dose is appropriated for perioperative prophylactic protocols and that given with a dose interval of 12 hours would be effective for susceptible infection treatment in cats.

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