scholarly journals Enhanced intestinal reabsorption due to reduced metabolism of ceftriaxone

2017 ◽  
Author(s):  
Tapas K Sar ◽  
Indranil Samanta ◽  
Rabindra N Hansda ◽  
Rinku Buragohain ◽  
Tapan K Mandal
Keyword(s):  
Single Dose ◽  
Half Life ◽  
Supportive Therapy ◽  
Pharmacokinetic Interaction ◽  
Time Schedule ◽  
Elimination Half ◽  
Lactating Goats ◽  
Absorption Phase ◽  
Plasma And Urine Samples ◽  
Predetermined Time

AbstractThe polyherbal drug (Fibrosin®) is often used as supportive therapy with intramuscular ceftriaxone injection for treatment of mastitis. A single dose of ceftriaxone at 50 mg kg−1 was administered intramuscularly in six healthy lactating goats and a single oral dose of Fibrosin® (1.9 gm) was given 1 hr prior to intramuscular ceftriaxone injection to study disposition of ceftriaxone. Plasma and urine samples were collected at predetermined time schedule and ceftriaxone/ceftizoxime was extracted and analyzed by HPLC. Ceftriaxone persisted for 3 hr in plasma of fibrosin treated healthy lactating goats. Mean t½ K (distribution half life) following absorption phase and t½ K′(elimination half life) following intestinal re-absorption phase were respectively, 0.091 ± 0.01 and 0.43 ± 0.03 hr with a re-absorption half life (t½Ka′) of 0.18 ± 0.003 hr.Ceftriaxone at a lower concentration (67.91 ± 9.42 μg ml−1) was recovered at 24 hr post dosing from urine. This is the first report of pharmacokinetic interaction of intramuscular ceftriaxone injection and the oral polyherbal drug (which was found to be a cytochrome P450 inhibitor).

scholarly journals Compartmental Pharmacokinetics and Tissue Drug Distribution of the Pradimicin Derivative BMS 181184 in Rabbits

1998 ◽  
Vol 42 (10) ◽  
pp. 2700-2705 ◽  
Author(s):  
Andreas H. Groll ◽  
Tin Sein ◽  
Vidas Petraitis ◽  
Ruta Petraitiene ◽  
Diana Callender ◽  
...  
Keyword(s):  
Single Dose ◽  
Half Life ◽  
Peak Plasma ◽  
Volume Of Distribution ◽  
Multiple Dosing ◽  
Time Curve ◽  
Dose Administration ◽  
Single Dose Administration ◽  
Elimination Half ◽  
Dose Dependent

ABSTRACT The pharmacokinetics of the antifungal pradimicin derivative BMS 181184 in plasma of normal, catheterized rabbits were characterized after single and multiple daily intravenous administrations of dosages of 10, 25, 50, or 150 mg/kg of body weight, and drug levels in tissues were assessed after multiple dosing. Concentrations of BMS 181184 were determined by a validated high-performance liquid chromatography method, and plasma data were modeled into a two-compartment open model. Across the investigated dosage range, BMS 181184 demonstrated nonlinear, dose-dependent kinetics with enhanced clearance, reciprocal shortening of elimination half-life, and an apparently expanding volume of distribution with increasing dosage. After single-dose administration, the mean peak plasma BMS 181184 concentration (C max) ranged from 120 μg/ml at 10 mg/kg to 648 μg/ml at 150 mg/kg; the area under the concentration-time curve from 0 to 24 h (AUC0–24) ranged from 726 to 2,130 μg · h/ml, the volume of distribution ranged from 0.397 to 0.799 liter/kg, and the terminal half-life ranged from 4.99 to 2.31 h, respectively (P < 0.005 toP < 0.001). No drug accumulation in plasma occurred after multiple daily dosing at 10, 25, or 50 mg/kg over 15 days, although mean elimination half-lives were slightly longer. Multiple daily dosing at 150 mg/kg was associated with enhanced total clearance and a significant decrease in AUC0–24 below the values obtained at 50 mg/kg (P < 0.01) and after single-dose administration of the same dosage (P < 0.05). Assessment of tissue BMS 181184 concentrations after multiple dosing over 16 days revealed substantial uptake in the lungs, liver, and spleen and, most notably, dose-dependent accumulation of the drug within the kidneys. These findings are indicative of dose- and time-dependent elimination of BMS 181184 from plasma and renal accumulation of the compound after multiple dosing.

scholarly journals Herb-Drug Pharmacokinetic Interaction of a Traditional Chinese Medicine Jia-Wei-Xiao-Yao-San with 5-Fluorouracil in the Blood and Brain of Rat Using Microdialysis

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Meng-Hsuan Chiang ◽  
Li-Wen Chang ◽  
Ju-Wen Wang ◽  
Lie-Chwen Lin ◽  
Tung-Hu Tsai
Keyword(s):  
Chinese Medicine ◽  
Half Life ◽  
High Performance ◽  
Pharmacokinetic Interaction ◽  
Volume Of Distribution ◽  
Research Database ◽  
Elimination Half Life ◽  
Elimination Half ◽  
Drug Pharmacokinetic ◽  
The Brain

According to a survey from the National Health Insurance Research Database (NHIRD), Jia-Wei-Xiao-Yao-San (JWXYS) is the most popular Chinese medicine for cancer patients in Taiwan. 5-Fluorouracil (5-FU) is a general anticancer drug for the chemotherapy. To investigate the herb-drug interaction of JWXYS on pharmacokinetics of 5-FU, a microdialysis technique coupled with a high-performance liquid chromatography system was used to monitor 5-FU in rat blood and brain. Rats were divided into four parallel groups, one of which was treated with 5-FU (100 mg/kg, i.v.) alone and the remaining three groups were pretreated with a different dose of JWXYS (600, 1200, or 2400 mg/kg/day for 5 consecutive days) followed by a combination with 5-FU. This study demonstrates that 5-FU with JWXYS (600 mg/kg/day or 1200 mg/kg/day) has no significant effect on the pharmacokinetics of 5-FU in the blood and brain. However, JWXYS (2400 mg/kg/day) coadministered with 5-FU extends the elimination half-life and increases the volume of distribution of 5-FU in the blood. The elimination half-life of 5-FU in the brain for the pretreatment group with 2400 mg/kg/day of JWXYS is significantly longer than that for the group treated with 5-FU alone and also reduces the clearance. This study provides practical dosage information for clinical practice and proves the safety of 5-FU coadministered with JWXYS.

Single-Dose Pegfilgrastim after Chemotherapy Is Highly Effective in Enhancing the Mobilization of Autologous CD34+ Peripheral Blood Stem Cells in Patients with Lymphoid Malignancies and Solid Tumors.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2922-2922
Author(s):  
Frank Kroschinsky ◽  
Kristina Hoelig ◽  
Uwe Platzbecker ◽  
Eberhard Schleyer ◽  
Rainer Ordemann ◽  
...  
Keyword(s):  
Stem Cells ◽  
Single Dose ◽  
Solid Tumors ◽  
Peripheral Blood ◽  
Half Life ◽  
Peripheral Blood Stem Cells ◽  
Elimination Half Life ◽  
Elimination Half ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract The administration of myelosuppressive chemotherapy followed by daily injections of granulocyte-colony stimulating factor (G-CSF) is the common procedure to mobilize autologous CD34+ peripheral blood stem cells (PBPC). Pegfilgrastim (NeulastaTM, Amgen Inc., Thousand Oaks, USA) is a covalent conjugate of filgrastim and polyethylene glycol with an increased elimination half-life due to decreased serum clearance. Whereas a single injection of pegfilgrastim (PEGFIL) has been shown to be equivalent to daily filgrastim in enhancing neutrophil recovery after chemotherapy, the experiences with PEGFIL in mobilization of PBPC are limited. We report 40 pts (22 male, 18 female, median age 53 years) who had a PBPC mobilization treatment for Hodgkin′s lymphoma (n=3), non-Hodgkin′s lymphoma (n=13), multiple myeloma (n=16), acute lymphoblastic leukaemia (n=3) or solid tumors (n=5). The mobilization regimen consisted of disease specific chemotherapy and a single subcutaneous injection of 6 mg PEGFIL administered 48 hours after the end of cytotoxic treatment (day 0). CD34+ cells in the peripheral blood (PB-CD34) were measured if white blood cells (WBC) exceeded 1.0 Gpt/L after nadir. PBPC collections started at a PB-CD34 cell count &gt;10/μl and were performed as large-volume apheresis (4x blood volume) using a Cobe Spectra (Gambro BCT Inc.). Additional conventional filgrastim (FIL) was given at a dose of 2x5μg/kg if PB-CD34 count was found to be &lt;10/μl. Blood samples for pharmacokinetics were taken in 9 pts. The median start of aphereses was on day +9 after the administration of PEGFIL and on day +15 after start of chemotherapy regimen, respectively. Median PB-CD34 peak was 74/μl (range 9–565/μl). The median PBPC yield was 7.6 x 10^6 CD34+ cells/kg (range 1.5–88.1). The target cell dose to be collected (≥ 2.5 x 10^6 CD34+ cells/kg) was achieved in 36 (90 %) pts, in 29 pts (72.5 %) ≥ 4.0 x 10^6 CD34+ cells/kg could be obtained with a single collection. Additional FIL administrations were necessary in 7 patients (17.5 %) for 2 to 6 days. All of them were heavily pretreated including a previous autologous transplant in two of these patients. PEGFIL was well tolerated except for moderate bone pain which occurred in all patients. The mean values (± SD) for peak plasma concentration of PEGFIL (cmax), time to reach the maximum plasma level (tmax) and elimination half-life (t1/2) were 154 (± 83) ng/ml, 56 (±21) hours and 23 (± 9) hours, respectively. We conclude that a single dose of 6 mg PEGFIL after chemotherapy is safe and highly effective in enhancing the mobilization of CD34+ PBPC for stem cell collection. Further investigations are warranted, including comparison with non-pegylated G-CSFs and in combination with antiadhesive agents.

Pharmacokinetics of retinyl palmitate and retinol after intramuscular retinyl palmitate administration in severe malaria

2000 ◽  
Vol 99 (5) ◽  
pp. 433-441 ◽  
Author(s):  
Timothy M. E. DAVIS ◽  
Tran Quang BINH ◽  
Le The Anh THU ◽  
Ric ROSSI ◽  
Phan Thi DANH ◽  
...  
Keyword(s):  
Severe Malaria ◽  
Half Life ◽  
Supportive Therapy ◽  
Indirect Evidence ◽  
Retinyl Palmitate ◽  
Adjunctive Treatment ◽  
Severe Illness ◽  
Serum Retinol ◽  
Elimination Half

Retinol (vitamin A alcohol) is an accepted adjunctive treatment in infections such as measles. There is also indirect evidence from in vitro, animal and human studies that retinol supplementation may be beneficial in severe malaria. There have, however, been no studies that have examined the pharmacokinetics of acute retinol supplementation in severe illness. To establish whether mobilization of intramuscular retinyl palmitate (RP) and its availability as retinol are adequate in complicated falciparum malaria, we administered a single dose of 400000 i.u. of RP to six Vietnamese adults with severe malaria. Another 28 patients were not given RP. All patients had blood samples taken over 96 h for RP and retinol assay using HPLC, and received conventional anti-malarial and supportive therapy. Admission serum retinol concentrations were below the lower limit of the reference range (< 1.0 µmol/l) in 74% of the 34 patients. In supplemented patients, analysis of serum RP between 0 and 96 h using a multi-compartmental model revealed a median (range) delay in mobilization of 6.9 h (0.7–15.1 h), a bioavailability of 55% (19–100%) and an elimination half-life of 13.5 h (4.2–23.7 h). The area under the serum retinol curve expressed as an absolute or percentage change from baseline was greater in supplemented than in unsupplemented patients (P < 0.05). The separation in median serum retinol concentrations in the two groups was maximal at 48 h. The model-derived retinol half-life [1.5 (0.7–15.8) h] suggested rapid uptake, metabolism and/or excretion. In conclusion, there is variable RP bioavailability in severe malaria, but a significant if delayed increase in serum retinol over that associated with recovery from the infection. In severe infections, RP supplementation appears simple, well tolerated and of potential benefit once anti-microbial and supportive therapy have been established.

scholarly journals Reversible Crystallization of Argatroban after Subcutaneous Application in Pigs

Thrombosis ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-6
Author(s):  
Mercedes Lopez ◽  
Goetz Nowak
Keyword(s):  
Half Life ◽  
Subcutaneous Tissue ◽  
Subcutaneous Administration ◽  
Extended Period ◽  
Thrombin Inhibitor ◽  
Elimination Half Life ◽  
Chromogenic Assay ◽  
Elimination Half ◽  
Absorption Phase ◽  
Dose Dependent

Argatroban is a thrombin inhibitor used as anticoagulant in patients with heparin-induced thrombocytopenia. It is usually administered as an intravenous bolus followed by infusion. Nevertheless, its pharmacokinetics after subcutaneous administration is unknown. The aim of this study was to assess the pharmacokinetics of two different formulations of argatroban in pigs after subcutaneous administration. Antithrombotic activity in plasma was determined by ecarin chromogenic assay. To visualize the formation of crystals, argatroban was administered to rats into the subcutaneous tissue exposed after removing the skin, and the injection site was photographed at different times. After subcutaneous administration of a sorbitol/ethanol formulation of argatroban in pigs was observed a slow absorption phase was followed by long-lasting levels of this inhibitor. Cmax and AUC(0-24) showed dose-dependent increases, while elimination half-life and tmax value did not change significantly with dose. In contrast, saline-dissolved argatroban showed a faster absorption phase followed by a shorter elimination half-life. Argatroban dissolved in sorbitol/ethanol leads to long-lasting plasma levels due to the formation and permanent dissolution of a crystalline depot at the injection place. This represents a simple way to deliver argatroban continuously over an extended period which can be beneficial for prophylaxis or treatment of chronic coagulations disorders.

scholarly journals Pharmacokinetics and Bioequivalence Evaluation of Cyclobenzaprine Tablets

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Tatiane Maria de Lima Souza Brioschi ◽  
Simone Grigoleto Schramm ◽  
Eunice Kazue Kano ◽  
Eunice Emiko Mori Koono ◽  
Ting Hui Ching ◽  
...  
Keyword(s):  
Single Dose ◽  
Half Life ◽  
Healthy Subjects ◽  
Pharmacokinetic Parameters ◽  
Blood Samples ◽  
Open Model ◽  
Elimination Half Life ◽  
Elimination Half ◽  
Overnight Fasting ◽  
Tablet Formulations

The purpose of this study was to investigate cyclobenzaprine pharmacokinetics and to evaluate bioequivalence between two different tablet formulations containing the drug. An open, randomized, crossover, single-dose, two-period, and two-sequence design was employed. Tablets were administered to 23 healthy subjects after an overnight fasting and blood samples were collected up to 240 hours after drug administration. Plasma cyclobenzaprine was quantified by means of an LC-MS/MS method. Pharmacokinetic parameters related to absorption, distribution, and elimination were calculated. Cyclobenzaprine plasma profiles for the reference and test products were similar, as well as absorption pharmacokinetic parameters AUC (reference: 199.4 ng∗h/mL; test: 201.6 ng∗h/mL), (reference: 7.0 ng/mL; test: 7.2 ng/mL), and (reference: 4.5 h; test: 4.6 h). Bioequivalence was evaluated by means of 90% confidence intervals for the ratio of AUC (93%–111%) and (93%–112%) values for test and reference products, which were within the 80%–125% interval proposed by FDA. Cyclobenzaprine pharmacokinetics can be described by a multicompartment open model with an average rapid elimination half-life () of 3.1 hours and an average terminal elimination half-life () of 31.9 hours.

scholarly journals Single-dose pharmacokinetics of thalidomide in human immunodeficiency virus-infected patients.

1997 ◽  
Vol 41 (12) ◽  
pp. 2797-2799 ◽  
Author(s):  
S C Piscitelli ◽  
W D Figg ◽  
B Hahn ◽  
G Kelly ◽  
S Thomas ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Single Dose ◽  
Adverse Effects ◽  
Half Life ◽  
Elimination Half Life ◽  
Elimination Half ◽  
Immunodeficiency Virus ◽  
The Mean ◽  
Standard Deviations

The pharmacokinetics of thalidomide in nine human immunodeficiency virus-infected patients were studied. Single doses of thalidomide were well absorbed, with mean peak concentrations (+/- standard deviations) of 1.17 +/- 0.21 and 3.47 +/- 1.14 microg/ml in the 100- and 300-mg dosing groups, respectively, and the mean elimination half-life was approximately 6 h. Adverse effects were mild, with drowsiness being reported for seven of nine patients.

scholarly journals Pharmacokinetic interaction of nitroxynil and cefoperazone in goats

2015 ◽  
Vol 4 (3) ◽  
pp. 291
Author(s):  
Mohamed El-hewaity
Keyword(s):  
Clinical Significance ◽  
Half Life ◽  
Pharmacokinetic Interaction ◽  
Concomitant Administration ◽  
Microbiological Assay ◽  
The Other ◽  
Blood Samples ◽  
Elimination Half Life ◽  
Systemic Bioavailability ◽  
Elimination Half

<p>The pharmacokinetic aspects of cefoperazone (CEFO) were investigated via intravenous (IV), and intramuscular (IM) injections in clinically healthy goats at a dose of 20 mg/kg b.wt. Goats were pre-treated with nitroxynil (25%) or nitroxynil (34%) subcutaneously in a dose 10 mg/kg b.wt, respectively. Cefoperazone was injected intramuscularly nine hours following anthelmintic administration, and blood samples were taken by jugular venipuncture at standardized intervals. Cefoperazone concentrations in serum were determined by microbiological assay technique. Goats pre-treated with nitroxynil (25%) or nitroxynil (34%) showed a significant decrease in serum cefoperazone level as compared to non-anthelmintic treated goats. The obtained data revealed that administration of nitroxynil in both concentrations negatively affected most of the cefoperazone parameters. In this respect, the elimination half-life T<sub>0.5(el)</sub>, C<sub>max</sub>, AUC, and the systemic bioavailability (F %) were significantly decreased in both groups of nitroxynil-treated goats compared to non-anthelmintic treated goats. On the other hand, there were no significance differences between both nitroxynil (25% and 34%) treated goats. Concomitant administration of nitroxynil (25% and 34%) with cefoperazone resulted in significant alterations in the disposition kinetic of cefoperazone in goats. Consequently, the interaction between nitroxynil and cefoperazone could be of clinical significance and may require monitoring and adjustment of cefoperazone dosage.</p>

scholarly journals Pharmacokinetics of tulathromycin in pregnant ewes (Ovis aries) challenged with Campylobacter jejuni

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256862
Author(s):  
Michael Yaeger ◽  
Jonathan P. Mochel ◽  
Zuowei Wu ◽  
Paul Plummer ◽  
Orhan Sahin ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Half Life ◽  
Peak Plasma ◽  
Fetal Liver ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Ovis Aries ◽  
Elimination Half Life ◽  
Elimination Half ◽  
Predetermined Time

The purpose of this study was to evaluate the pharmacokinetics of tulathromycin in the plasma and maternal and fetal tissues of pregnant ewes when administered within 24 hours of a single, IV Campylobacter jejuni (C. jejuni) challenge. Twelve, pregnant ewes between 72–92 days of gestation were challenged IV with C. jejuni IA3902 and then treated with 1.1 ml/45.36 kg of tulathromycin subcutaneously 18 hours post-challenge. Ewes were bled at predetermined time points and euthanized either at a predetermined time point or following the observation of vaginal bleeding or abortion. Following euthanasia, tissues were collected for bacterial culture, pharmacokinetics and histologic examination. The maximum (geometric) mean tulathromycin plasma concentration was estimated at 0.302 μg/mL, with a peak level observed at around 1.2 hours. The apparent systemic clearance of tulathromycin was estimated at 16.6 L/h (or 0.28 L/kg/h) with an elimination half-life estimated at approximately 22 hours. The mean tissue concentrations were highest in the uterus (2.464 μg/g) and placentome (0.484 μg/g), and were lowest in fetal liver (0.11 μg/g) and fetal lung (0.03 μg/g). Compared to previous reports, results of this study demonstrate that prior IV administration of C. jejuni appeared to substantially alter the pharmacokinetics of tulathromycin, reducing both the peak plasma concentrations and elimination half-life. However, additional controlled trials are required to confirm those observations.

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