scholarly journals Plasma pharmacokinetics, tissue concentrations and urine elimination after cephalothin intravenous administration to cats under surgical conditions

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Gabriela A. Albarellos ◽  
Laura Montoya ◽  
Martín P. Lupi ◽  
Sabrina M. Passini ◽  
Paula Lorenzini ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
Plasma Concentrations ◽  
Dose Interval ◽  
Pharmacokinetic Profile ◽  
Wide Distribution ◽  
Tissue Concentrations ◽  
Initial Plasma ◽  
Plasma Pharmacokinetics ◽  
Prophylactic Use ◽  
Surgical Conditions

Pharmacokinetic profile, tissue concentrations and urine elimination of cephalothin in cats under surgical conditions after a single intravenous dose (30 mg/kg) were studied. Initial plasma concentrations were high [Cp(0), 353.79±118.92 μg/mL], with fast and moderately wide distribution [T1⁄2(d) 0.14±0.10 h] [V(d(ss)) 0.19±0.03 L/kg] and rapid elimination (ClB, 0.16±0.03 L/h.kg; T1⁄2, 1.07±0.23 h; MRT, 1.16±0.21 h). Thirty to 60 minutes after intravenous administration, cephalothin tissue concentrations were in the range of 3.73 μg/g (testicle tissue) to 25.63 μg/g (uterus). Tissue/plasma concentrations rate was in a range of 0.04 (testicle) to 0.21 (uterus). Cephalothin urine elimination was 66.49% in the first 6 hours after administration. Cephalothin plasma concentrations remained above a MIC≥1 μg/mL up to 5.5 hours in all the studied cats. However, for MIC≥8 –μg/mL (MIC breakpoint) this time is reduced to 2.5 hours. This suggests that proper perioperative prophylactic use of cephalothin in cats requires a dose interval not longer than 2 hours.

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.

Cefazolin pharmacokinetics in cats under surgical conditions

2016 ◽  
Vol 19 (10) ◽  
pp. 992-997 ◽  
Author(s):  
Gabriela A Albarellos ◽  
Laura Montoya ◽  
Sabrina M Passini ◽  
Martín P Lupi ◽  
Paula M Lorenzini ◽  
...  
Keyword(s):  
Half Life ◽  
Subcutaneous Tissue ◽  
Plasma Concentrations ◽  
Pharmacokinetic Profile ◽  
Intravenous Dose ◽  
Pharmacokinetic Parameters ◽  
Antibiotic Administration ◽  
Single Intravenous Dose ◽  
Tissue Concentrations ◽  
Surgical Conditions

Objectives The aim of this study was to determine the plasma pharmacokinetic profile, tissue concentrations and urine elimination of cefazolin in cats under surgical conditions after a single intravenous dose of 20 mg/kg. Methods Intravenous cefazolin (20 mg/kg) was administered to nine young mixed-breed cats 30 mins before they underwent surgical procedures (ovariectomy or orchiectomy). After antibiotic administration, samples from blood, some tissues and urine were taken. Cefazolin concentrations were determined in all biological matrices and pharmacokinetic parameters were estimated. Results Initial plasma concentrations were high (Cp(0), 134.80 ± 40.54 µg/ml), with fast and moderately wide distribution (distribution half-life [t½(d)] 0.16 ± 0.15 h; volume of distribution at steady state [V(d[ss])] 0.29 ± 0.10 l/kg) and rapid elimination (body clearance [ClB], 0.21 ± 0.06 l/h/kg; elimination half-life [t½], 1.18 ± 0.27 h; mean residence time 1.42 ± 0.36 h). Thirty to 60 mins after intravenous administration, cefazolin tissue concentrations ranged from 9.24 µg/ml (subcutaneous tissue) to 26.44 µg/ml (ovary). The tissue/plasma concentration ratio ranged from 0.18 (muscle) to 0.58 (ovary). Cefazolin urine concentrations were high with 84.2% of the administered dose being eliminated in the first 6 h postadministration. Conclusions and relevance Cefazolin plasma concentrations remained above a minimum inhibitory concentration of ⩽2 µg/ml up to 4 h in all the studied cats. This suggests that a single intravenous dose of 20 mg/kg cefazolin would be adequate for perioperative prophylactic use in cats.

scholarly journals Penetration of Piperacillin/Tazobactam Into Gynecologic Tissues Following a Single Loading Dose Prior to Hysterectomy

1994 ◽  
Vol 2 (1) ◽  
pp. 20-24
Author(s):  
William F. O'Brien ◽  
Shelley George
Keyword(s):  
Intravenous Administration ◽  
Genital Tract ◽  
Plasma Concentrations ◽  
Female Genital Tract ◽  
Loading Dose ◽  
Effective Agent ◽  
Tissue Concentrations ◽  
Tissue Samples ◽  
Single Intravenous Administration ◽  
Female Genital

Objective:This study was undertaken to determine plasma and pelvic tissue concentrations of piperacillin/tazobactam following a single intravenous administration.Methods:Plasma and tissue samples were obtained following administration of 3 g of piperacillin and 0.375 g of tazobactam. Concentrations of these agents were determined by chromatography.Results:Plasma concentrations (mean ±SD) for piperacillin/tazobactam were 208 ± 87/27 ± 8 and 95 ± 53/14 ± 2, respectively, at 30 and 60 min after the start of the infusion. The 8:1 ratio between piperacillin and tazobactam in plasma remained constant for up to 96 min. Tissue concentrations yielded a broader range, but each agent achieved significant penetration in each of the tissues studied.Conclusions:Piperacillin/tazobactam demonstrates favorable penetration in female genital tract tissues and Should be considered a potentially effective agent for female pelvic infections.

IMPACT probability of poor outcome and plasma cytokine concentrations are associated with multiple organ dysfunction syndrome following traumatic brain injury

2019 ◽  
Vol 131 (6) ◽  
pp. 1931-1937 ◽  
Author(s):  
Sungho Lee ◽  
Hyunsoo Hwang ◽  
Jose-Miguel Yamal ◽  
J. Clay Goodman ◽  
Imoigele P. Aisiku ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Organ Dysfunction ◽  
Multiple Organ Dysfunction Syndrome ◽  
Sofa Score ◽  
Plasma Concentrations ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction ◽  
Poor Outcome ◽  
Initial Plasma

OBJECTIVETraumatic brain injury (TBI) is a major cause of morbidity and mortality. Multiple organ dysfunction syndrome (MODS) occurs frequently after TBI and independently worsens outcome. The present study aimed to identify potential admission characteristics associated with post-TBI MODS.METHODSThe authors performed a secondary analysis of a recent randomized clinical trial studying the effects of erythropoietin and blood transfusion threshold on neurological recovery after TBI. Admission clinical, demographic, laboratory, and imaging parameters were used in a multivariable Cox regression analysis to identify independent risk factors for MODS following TBI, defined as maximum total Sequential Organ Failure Assessment (SOFA) score > 7 within 10 days of TBI.RESULTSTwo hundred patients were initially recruited and 166 were included in the final analysis. Respiratory dysfunction was the most common nonneurological organ system dysfunction, occurring in 62% of the patients. International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) probability of poor outcome at admission was significantly associated with MODS following TBI (odds ratio [OR] 8.88, 95% confidence interval [CI] 1.94–42.68, p < 0.05). However, more commonly used measures of TBI severity, such as the Glasgow Coma Scale, Injury Severity Scale, and Marshall classification, were not associated with post-TBI MODS. In addition, initial plasma concentrations of interleukin (IL)–6, IL-8, and IL-10 were significantly associated with the development of MODS (OR 1.47, 95% CI 1.20–1.80, p < 0.001 for IL-6; OR 1.26, 95% CI 1.01–1.58, p = 0.042 for IL-8; OR 1.77, 95% CI 1.24–2.53, p = 0.002 for IL-10) as well as individual organ dysfunction (SOFA component score ≥ 1). Finally, MODS following TBI was significantly associated with mortality (OR 5.95, 95% CI 2.18–19.14, p = 0.001), and SOFA score was significantly associated with poor outcome at 6 months (Glasgow Outcome Scale score < 4) when analyzed as a continuous variable (OR 1.21, 95% CI 1.06–1.40, p = 0.006).CONCLUSIONSAdmission IMPACT probability of poor outcome and initial plasma concentrations of IL-6, IL-8, and IL-10 were associated with MODS following TBI.

Design, Synthesis, and Pharmacokinetic Evaluation of O-Carbamoyl Tizoxanide Prodrugs

2020 ◽  
Vol 16 ◽  
Author(s):  
Xi He ◽  
Wenjun Hu ◽  
Fanhua Meng ◽  
Xingzhou Li
Keyword(s):  
Plasma Concentration ◽  
Broad Spectrum ◽  
Plasma Concentrations ◽  
Antiviral Drug ◽  
Systemic Exposure ◽  
Pharmacokinetic Profile ◽  
Hydroxyl Group ◽  
First Pass

Background: The broad-spectrum antiparasitic drug nitazoxanide (N) has been repositioned as a broad-spectrum antiviral drug. Nitazoxanide’s in vivo antiviral activities are mainly attributed to its metabolitetizoxanide, the deacetylation product of nitazoxanide. In reference to the pharmacokinetic profile of nitazoxanide, we proposed the hypotheses that the low plasma concentrations and the low system exposure of tizoxanide after dosing with nitazoxanide result from significant first pass effects in the liver. It was thought that this may be due to the unstable acyloxy bond of nitazoxanide. Objective: Tizoxanide prodrugs, with the more stable formamyl substituent attached to the hydroxyl group rather than the acetyl group of nitazoxanide, were designed with the thought that they might be more stable in plasma. It was anticipated that these prodrugs might be less affected by the first pass effect, which would improve plasma concentrations and system exposure of tizoxanide. Method: These O-carbamoyl tizoxanide prodrugs were synthesized and evaluated in a mouse model for pharmacokinetic (PK) properties and in an in vitro model for plasma stabilities. Results: The results indicated that the plasma concentration and the systemic exposure of tizoxanide (T) after oral administration of O-carbamoyl tizoxanide prodrugs were much greater than that produced by equimolar dosage of nitazoxanide. It was also found that the plasma concentration and the systemic exposure of tizoxanide glucuronide (TG) were much lower than that produced by nitazoxanide. Conclusion: Further analysis showed that the suitable plasma stability of O-carbamoyl tizoxanide prodrugs is the key factor in maximizing the plasma concentration and the systemic exposure of the active ingredient tizoxanide.

Lack of Analgesic Activity of Morphine-6-glucuronide after Short-term Intravenous Administration in Healthy Volunteers 

1997 ◽  
Vol 87 (6) ◽  
pp. 1348-1358 ◽  
Author(s):  
Jorn Lotsch ◽  
Gerd Kobal ◽  
Anne Stockmann ◽  
Kay Brune ◽  
Gerd Geisslinger ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Analgesic Activity ◽  
Intravenous Administration ◽  
Opioid Analgesic ◽  
Plasma Concentrations ◽  
Experimental Pain ◽  
Controlled Study ◽  
Short Term ◽  
Analgesic Effects ◽  
Relative Contribution

Background The analgesic activity of morphine-6-glucuronide (M-6-G) is well recognized for its contribution to the effects of morphine and its possible use as an opioid analgesic with a wider therapeutic range than morphine. The present study attempted to quantify the relative contribution of M-6-G to analgesia observed after systemic administration of morphine. Methods In a placebo-controlled, sixfold crossover study in 20 healthy men, the effects of M-6-G were assessed at steady-state plasma concentrations of M-6-G identical to and two and three times higher than those measured after administration of morphine. Morphine and M-6-G were administered as an intravenous bolus followed by infusion over 4 h. Dosage A was M-6-G-bolus of 0.015 mg/kg plus infusion of 0.0072 mg x kg(-1) x h(-1). Dosage B was M-6-G-bolus of 0.029 mg/kg plus infusion of 0.014 mg x kg(-1) x h(-1). Dosage C was M-6-G-bolus of 0.044 mg/kg plus infusion of 0.022 mg x kg(-1) x h(-1). Dosage D was a morphine bolus of 0.14 mg/kg plus infusion of 0.05 mg x kg(-1) x h(-1) for 4 h. Dosage E was M-6-G combined with morphine (doses A + D). Dosage F was a placebo. The analgesic effects of M-6-G and morphine were measured before administration of the bolus and after 3.5 h using an experimental pain model based on pain-related cortical potentials and pain ratings after specific stimulation of the nasal nociceptor with short pulses of gaseous carbon dioxide. Results Morphine significantly reduced subjective and objective pain correlates compared with placebo. In contrast, M-6-G produced no statistically significant effects. The addition of M-6-G to morphine did not increase the effects of morphine. Morphine produced significantly more side effects than M-6-G. Conclusion After short-term intravenous administration at doses that produce plasma concentrations of M-6-G similar to those seen after administration of morphine, M-6-G had no analgesic effects in the present placebo-controlled study in healthy volunteers.

scholarly journals The intravenous pharmacokinetics of diminazene in healthy dogs

2009 ◽  
Vol 80 (4) ◽  
Author(s):  
V. Naidoo ◽  
M.S.G. Mulders ◽  
G.E. Swan
Keyword(s):  
Plasma Concentrations ◽  
Compartmental Analysis ◽  
Central Compartment ◽  
Volume Of Distribution ◽  
Time Profile ◽  
Secondary Peak ◽  
German Shepherd ◽  
Plasma Pharmacokinetics ◽  
Healthy Dogs ◽  
Over 40 Years

Diminazene remains one of South Africa's most commonly used antiprotozoal agents for the management of babesiosis in dogs . Although the drug has been on the market for over 40 years, its intravenous pharmacokinetics are poorly known. To better understand the pharmacokinetics of the drug Berenil®, it was reconstituted in sterile water and administered intravenously to 6 adult German shepherd dogs. All 6 dogs demonstrated the previously described secondary peak in the plasma concentration versus time profile. The plasma pharmacokinetics for diminazene are described by both non-compartmental and compartmental models. From non-compartmental analysis, the area under curve to the last sample point (AUClast), clearance (CL) and volume of distribution (Vz) were 4.65±1.95 ng/mℓ/h, 0.77±0.18 ℓ/kg/h and 2.28±0.60 ℓ/kg, respectively. For compartmental modelling, the plasma concentrations were fitted to both a 2-compartmental open model and a recirculatory enterohepatic model. From the recirculation model, the rate of release and re-entry into the central compartment varied markedly with the rate of release from the gall bladder (Ttom) being estimated at 27 ± 20.90 h. Once released, drug re-entry into the central compartment was variable at 9.70±5.48 h. With normal biliary excretion time being about 2 h, this indicates that the redistribution cannot be occurring physiologically from the bile. Although it was not possible to identify the site from which sequestration and delayed release is occurring, it is believed that it is most likely from the liver. The study therefore showed that the secondary peak described for the pharmacokinetics of intramuscular administered diminazene in the dog is not related to biphasic absorption.

Influence of Anthropometric Characteristics in Patients With Her2-Positive Breast Cancer on Initial Plasma Concentrations of Trastuzumab

2017 ◽  
Vol 51 (11) ◽  
pp. 976-980 ◽  
Author(s):  
Jonathan González García ◽  
Fernando Gutiérrez Nicolás ◽  
Gloria Julia Nazco Casariego ◽  
José Norberto Batista López ◽  
Isaac Ceballos Lenza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Standard Dose ◽  
Plasma Concentrations ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Initial Plasma ◽  
Anthropometric Characteristics ◽  
Secondary Objective ◽  
Positive Breast Cancer

Background: Plasma concentrations of trastuzumab <20 µg/mL in patients with gastric cancer are associated with reduced progression-free and overall survival. In breast cancer treatment, this relationship has not yet been studied, but a suboptimal pharmacodynamic exposure to trastuzumab could be a reason for therapeutic failure of treatment of HER2-positive breast cancer. Objective: The objective of the present study was to determine the proportion of nonmetastatic HER2-positive breast cancers that do not reach a minimum plasma concentration ( Cmin) of 20 µg/mL after first drug administration, established as therapeutically effective in clinical trials. The secondary objective was to identify the physiological and anthropometric characteristics that determine interindividual pharmacokinetic variability. Methods: Serum concentrations of trastuzumab were assessed by ELISA on day 1 of the second cycle before administration of the second dose ( Cmin). Results: Of 19 patients included, 9 (47.4%) had a mean Cmin of 19.0 µg/mL (±12.1) after the first administration. Body mass index (BMI) and weight was the main variable that determined the achievement of therapeutic levels after the first administration. Thus, the proportion of patients reaching the target concentration was 89% when BMI was ≤30 kg/m2 but only 11% when BMI was >30 kg/m2 ( P < 0.01). Conclusions: The standard dose of 600 mg subcutaneous trastuzumab did not ensure adequate pharmacodynamic exposure from the first administration in 52% of patients, with weight and BMI being related to the plasma levels obtained.

scholarly journals The tablet formulation of posaconazole: clinical pharmacology and the use in patients with hematologic malignancies

2020 ◽  
Vol 22 (2) ◽  
pp. 96-117
Author(s):  
Alexander V. Veselov
Keyword(s):  
Clinical Studies ◽  
Fungal Infections ◽  
Plasma Concentrations ◽  
Pharmacokinetic Profile ◽  
Hematologic Malignancies ◽  
Tablet Formulation ◽  
Oral Suspension ◽  
Tolerability Profile ◽  
Hematopoietic Stem ◽  
Release Tablet

Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various fungi, including yeast and molds, including Mucorales, what makes a key difference with itraconazole and voriconazole. Clinical studies have demonstrated his efficacy for prophylaxis against invasive fungal infections in hematological patients at high risk (with acute myeloid leukemia, myelodysplastic syndrome, aplastic anemia, and in patients after hematopoietic stem cell transplantation, especially with graft versus host disease). Posaconazole also use as salvage therapy against invasive aspergillosis, mucormycosis and some other systemic mycoses. For today there are 3 posaconazole formulations – oral suspension, modify release tablet and intravenous solution (not registered in Russia at the time of writing this paper). As far as bioavailability of posaconazole following administration by oral suspension is highly variable with low unstable plasma concentrations and there are number of factors with negatively influence to the pharmacokinetic profile of suspension a delayed-release tablet was developed using hot-melt extrusion technology with a pH-sensitive polymer. The tablet formulation releases the drug in the intestine, and this leads to the enhanced bioavailability and increased posaconazole exposure parameters and, as a result, to a higher efficacy. This was demonstrated in pre-clinical, early phase clinical studies and confirmed with data from real practice. The tablet formulation has well tolerability profile with a low incidence of clinically significant adverse events. For today posaconazole included in all relevant clinical recommendations with high levels of evidence, including prophylaxis of invasive mycoses and therapy of their refractory forms, while the authors agree that for the oral therapy a preference should be given to the tablet formulation of posaconazole.

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