scholarly journals Pharmacokinetics, urinary excretion and plasma protein binding of ofloxacin in water buffalo calves (Bubalus bubalis)

2013 ◽  
Vol 84 (1) ◽  
Author(s):  
Ajay K. Ola ◽  
Harpal S. Sandhu ◽  
Vinod K. Dumka ◽  
Bibhuti Ranjan
Keyword(s):  
Urinary Excretion ◽  
Half Life ◽  
High Performance ◽  
Water Buffalo ◽  
Plasma Concentrations ◽  
Pharmacokinetic Profile ◽  
Volume Of Distribution ◽  
Peripheral Compartment ◽  
Buffalo Calves ◽  
Time Curve

Pharmacokinetics and urinary excretion of an intravenous dose of 5 mg.kg–1 ofloxacin were investigated in water buffalo calves. Plasma concentrations of ofloxacin were determined by high-performance liquid chromatography. Ofloxacin was rapidly distributed from the central to the peripheral compartment as evidenced by a short distribution half-life (0.09 h ± 0.003 h) and high K12 (4.7 h–1 ± 0.1 h–1), and was detected in plasma for 8 h. The large volume of distribution (2.48 L.kg–1 ± 0.18 L.kg–1) obtained in this study indicated high distribution of ofloxacin in water buffalo calves. The elimination half-life, the area under the plasma drug concentration–time curve and total body clearance were 2.11 h ± 0.13 h, 6.20 µg.mL—1 ± 0.23 µg.mL—1.h and 0.81 mL.kg–1.h–1 ± 0.03 mL.kg–1.h–1, respectively. About 18.7% of administered drug was bound to plasma proteins and approximately 32.5% of the administered dose was recovered in urine within 48 h. The results of the study indicated a favourable pharmacokinetic profile of ofloxacin in water buffalo calves, which suggests that ofloxacin may be effective against urinary pathogens in this species.

scholarly journals Influences of tolfenamic acid and flunixin meglumine on the disposition kinetics of levofloxacin in sheep

2020 ◽  
Vol 68 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Duygu Durna Corum ◽  
Orhan Corum ◽  
Ramazan Yildiz ◽  
Hatice Eser Faki ◽  
Merve Ider ◽  
...  
Keyword(s):  
Half Life ◽  
High Performance ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Tolfenamic Acid ◽  
Time Curve ◽  
Inflammatory Conditions ◽  
Flunixin Meglumine ◽  
Model Following ◽  
Elimination Half

AbstractThe pharmacokinetics of levofloxacin (4 mg/kg), administered both alone and in combination with tolfenamic acid (2 mg/kg) and flunixin meglumine (2.2 mg/kg), was established after intravenous administration in sheep. Plasma levofloxacin concentrations were assayed by high-performance liquid chromatography and analysed according to the two-compartment open model. Following the administration of levofloxacin alone, the mean distribution half-life, elimination half-life, total clearance, volume of distribution at steady state and area under the plasma concentration–time curve were 0.20 h, 1.82 h, 0.39 L/h/kg, 0.96 L/kg and 10.40 h × µg/mL, respectively. Tolfenamic acid and flunixin meglumine caused a slow elimination and increased plasma concentrations of levofloxacin in combination administration. Levofloxacin, with an alteration in the dosage regimen, can be used effectively with tolfenamic acid and flunixin meglumine for the therapy of infections and inflammatory conditions in sheep.

Pharmacokinetics and metabolism of epidoxorubicin and doxorubicin in humans.

1988 ◽  
Vol 6 (3) ◽  
pp. 517-526 ◽  
Author(s):  
K Mross ◽  
P Maessen ◽  
W J van der Vijgh ◽  
H Gall ◽  
E Boven ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Urinary Excretion ◽  
Half Life ◽  
Enterohepatic Circulation ◽  
Plasma Concentrations ◽  
Parent Drug ◽  
Volume Of Distribution ◽  
Maximum Plasma ◽  
Cumulative Urinary Excretion ◽  
Second Peak

Pharmacokinetics of doxorubicin (DOX), epidoxorubicin (EPI), and their metabolites in plasma have been performed in eight patients receiving 40 to 56 mg/m2 of both anthracyclines as a bolus injection in two sequential cycles. Terminal half-life and volume of distribution appeared to be smaller in case of EPI, whereas plasma clearance and cumulative urinary excretion was larger in comparison to DOX. The major metabolite of DOX was doxorubicinol (Aol) followed by 7-deoxy-doxorubicinol (7d-Aolon). Metabolism to glucuronides was found in case of EPI only. The area under the curves (AUC) of the metabolites of EPI decreased in the order of the glucoronides E-glu greater than Eol-glu, 7d-Aolon greater than epirubicinol (Eol). The AUC of Eol was half of the value in its counterpart Aol. In the case of EPI, the AUC of 7d-Aolon was twice the level of that of the corresponding metabolite of DOX. The terminal half-lives of the cytostatic metabolites Aol and Eol were similar, but longer than the corresponding values of their parent drugs. Half-lives of the glucuronides (E-glu, Eol-glu) were similar to the half-life of their parent drug. 7d-Aolon had a somewhat shorter half-life in comparison to both DOX and EPI. Approximately 6.2% of EPI and 5.9% of DOX were excreted by the kidney during the initial 48 hours. Aol was found in the urine of patients treated with DOX, whereas Eol, E-glu, and Eol-glu were detected in urine of patients treated with EPI. The cumulative urinary excretion appeared to be 10.5% for EPI and its metabolites, and 6.9% for DOX and its metabolite. The plasma concentration v time curves of (7d)-aglycones showed a second peak between two and 12 hours after injection, suggesting an enterohepatic circulation for metabolites lacking the daunosamine sugar moiety. The plasma concentrations of the glucuronides were maximal at 1.2 hours for E-glu and 1.9 hours for Eol-glu. All other compounds reached their maximum plasma concentration during the first minutes after the administration of DOX and EPI. Deviating plasma kinetics were observed in one patient, probably due to prior drug administration.

Dose escalation of cyclophosphamide in patients with breast cancer: consequences for pharmacokinetics and metabolism.

1997 ◽  
Vol 15 (5) ◽  
pp. 1885-1896 ◽  
Author(s):  
D Busse ◽  
F W Busch ◽  
F Bohnenstengel ◽  
M Eichelbaum ◽  
P Fischer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dose Escalation ◽  
High Performance ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
High Dose ◽  
31P Nmr Spectroscopy ◽  
Metabolic Clearance ◽  
Time Curve ◽  
Relative Contribution

PURPOSE The alkylating anticancer agent cyclophosphamide (CP) is a prodrug that undergoes a complex metabolism in humans producing both active and inactive metabolites. In parallel, unchanged CP is excreted via the kidneys. The aim of this study was to investigate the influence of dose escalation on CP pharmacokinetics and relative contribution of activating and inactivating elimination pathways. PATIENTS AND METHODS Pharmacokinetics of CP were assessed in 12 patients with high-risk primary breast cancer who received an adjuvant chemotherapy regimen that included four courses of conventional-dose CP (500 mg/m2 over 1 hour every 3 weeks) followed by one final course of high-dose CP (100 mg/kg over 1 hour). Plasma concentrations of CP were analyzed by high-performance liquid chromatography (HPLC), 24-hour urinary concentrations of CP, and its inactive metabolites (carboxyphosphamide, dechloroethylcyclophosphamide [dechlorethylCP], ketocyclophosphamide [ketoCP]) were determined by 31-phosphorus-nuclear magnetic resonance (31P-NMR)-spectroscopy. RESULTS There was no difference in dose-corrected area under the concentration-time curve (AUC) (216 v 223 [mumol.h/[mL.g]), elimination half-life (4.8 v 4.8 hours), systemic clearance (79 v 77 mL/min) and volume of distribution (0.49 v 0.45 L/kg) of CP between conventional- and high-dose therapy, respectively. However, during high-dose chemotherapy, we observed a significant increase in the renal clearance of CP (15 v 23 mL/min; P < .01) and in the formation clearance of carboxyphosphamide (7 v 12 mL/min; P < .05) and dechloroethylCP (3.2 v 4.2 mL/min; P < .05), whereas metabolic clearance to ketoCP remained unchanged (1.3 v 1.2 mL/min). Consequently, metabolic clearance to the remaining (reactive) metabolites decreased from 52 to 38 mL/min (P < .001). The relative contribution of the different elimination pathways to overall clearance of CP demonstrated wide interindividual variability. CONCLUSION Overall pharmacokinetics of CP are apparently not affected during eightfold dose escalation. However, there is a shift in the relative contribution of different clearances to systemic CP clearance in favor of inactivating elimination pathways, thereby indicating saturation of bioactivating enzymes during dose escalation. Besides individual enzyme capacity, hydration and concomitant medication with dexamethasone modulated CP disposition.

scholarly journals Meropenem Plasma and Interstitial Soft Tissue Concentrations in Obese and Nonobese Patients—A Controlled Clinical Trial

Antibiotics ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 931
Author(s):  
Philipp Simon ◽  
David Petroff ◽  
David Busse ◽  
Jana Heyne ◽  
Felix Girrbach ◽  
...  
Keyword(s):  
Half Life ◽  
High Performance ◽  
Subcutaneous Tissue ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Volume Of Distribution ◽  
Controlled Clinical Trial ◽  
Morbidly Obese ◽  
Maximum Plasma ◽  
The Impact

Background: This controlled clinical study aimed to investigate the impact of obesity on plasma and tissue pharmacokinetics of meropenem. Methods: Obese (body mass index (BMI) ≥ 35 kg/m2) and age-/sex-matched nonobese (18.5 kg/m2 ≥ BMI ≤ 30 kg/m2) surgical patients received a short-term infusion of 1000-mg meropenem. Concentrations were determined via high performance liquid chromatography-ultraviolet (HPLC-UV) in the plasma and microdialysate from the interstitial fluid (ISF) of subcutaneous tissue up to eight h after dosing. An analysis was performed in the plasma and ISF by noncompartmental methods. Results: The maximum plasma concentrations in 15 obese (BMI 49 ± 11 kg/m2) and 15 nonobese (BMI 24 ± 2 kg/m2) patients were 54.0 vs. 63.9 mg/L (95% CI for difference: −18.3 to −3.5). The volume of distribution was 22.4 vs. 17.6 L, (2.6–9.1), but the clearance was comparable (12.5 vs. 11.1 L/h, −1.4 to 3.1), leading to a longer half-life (1.52 vs. 1.31 h, 0.05–0.37) and fairly similar area under the curve (AUC)8h (78.7 vs. 89.2 mg*h/L, −21.4 to 8.6). In the ISF, the maximum concentrations differed significantly (12.6 vs. 18.6 L, −16.8 to −0.8) but not the AUC8h (28.5 vs. 42.0 mg*h/L, −33.9 to 5.4). Time above the MIC (T > MIC) in the plasma and ISF did not differ significantly for MICs of 0.25–8 mg/L. Conclusions: In morbidly obese patients, meropenem has lower maximum concentrations and higher volumes of distribution. However, due to the slightly longer half-life, obesity has no influence on the T > MIC, so dose adjustments for obesity seem unnecessary.

scholarly journals Pharmacokinetics of a Single Bolus of Propofol in Chinese Children of Different Ages

2006 ◽  
Vol 104 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Wang Ning ShangGuan ◽  
QingQuan Lian ◽  
Leon Aarons ◽  
Ivan Matthews ◽  
ZengShou Wang ◽  
...  
Keyword(s):  
High Performance ◽  
Plasma Concentrations ◽  
Pharmacokinetic Profile ◽  
Volume Of Distribution ◽  
Chinese Children ◽  
Average Weight ◽  
Single Bolus ◽  
Arterial Blood ◽  
Different Ages ◽  
Distribution Parameters

Background There is no information about the pharmacokinetic profile of propofol in Chinese children younger than 3 yr. This study was designed to determine a complete pharmacokinetic profile of a single dose of propofol in Chinese children of different ages. Methods Arterial blood samples were obtained from 35 children with an American Society of Anesthesiologist physical status of I or II at 2, 4, 6, 8, 10, 20, 30, 45, 60, 90, 120, and 180 min after a single bolus intravenous injection of propofol (3 mg/kg). The plasma concentrations of propofol were measured using high-performance liquid chromatography with an ultraviolet detector. A population model was used to estimate the pharmacokinetics of propofol. Results A three-compartment pharmacokinetic model best described the pharmacokinetics of propofol. Clearance was 0.185 l/min, the volume of distribution of the central compartment was 7.41 l, the peripheral volumes of distribution were 54.6 and 7.2 l, and the intercompartmental clearances were 0.614 and 0.692 l/min for a child of the average weight of 13.7 kg. The half-lives were 2.67, 14.89, and 310.60 min. Covariate models were applied, and weight was found to be significant covariate for the clearance and volume of distribution parameters. No significant age effect could be demonstrated on clearance or volume of distribution parameters after weight was taken into account. Conclusions This study supports the case that the pharmacokinetic properties of propofol do not differ substantially across Chinese children of different ages after weight has been accounted for.

scholarly journals Pharmacokinetics of Lornoxicam in rabbits after single intravenous bolus and intramuscular administrations

2016 ◽  
Vol 4 (1) ◽  
pp. 66
Author(s):  
Abubakr El-Mahmoudy
Keyword(s):  
Plasma Concentration ◽  
Half Life ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Plasma Concentrations ◽  
Pharmacokinetic Profile ◽  
Volume Of Distribution ◽  
Bolus Administration ◽  
Systemic Bioavailability ◽  
Total Body

The pharmacokinetics of lornoxicam (a non-steroidal anti-inflammatory drug) at a dose of 0.4 mg/Kg body weight was evaluated after single intravenous (i.v.) and intramuscular (i.m.) bolus administrations in rabbits. An HPLC assay using pure lornoxicam base as a standard was used to measure its concentrations in plasma at prefixed time points up to 12 hours post administration. Following an i.v. bolus injection, the plasma concentration-time curves of lornoxicam were best represented by two-compartment open model. The drug was rapidly distributed and moderately eliminated with half-lives of distribution (t1/2α) and elimination (t1/2β) of 0.238 and 2.611 h, respectively. The volume of distribution was large with (Vdss) value of 1.499 L. The total body clearance (ClB) was 0.413 L/h. After i.m. bolus administration of the same dose, lornoxicam was moderately and completely absorbed in rabbits with an absorption half-life (t½ab) of 1.228 h with peak plasma concentration (Cmax) of 0.463 μg/mL attained at 1.512 h (Tmax) and systemic bioavailability of 99.79%. The elimination half-life following i.m. administration was 2.283 h. The extent of plasma protein binding percent was 98.9%. The study recommends the use of lornoxicam in rabbits because of its good pharmacokinetic profile indicated by good absorption, bioavailability and plasma concentrations.

Pharmacokinetics and bioequivalence of etoposide following intravenous administration of etoposide phosphate and etoposide in patients with solid tumors.

1995 ◽  
Vol 13 (11) ◽  
pp. 2835-2841 ◽  
Author(s):  
S Kaul ◽  
L N Igwemezie ◽  
D J Stewart ◽  
S Z Fields ◽  
M Kosty ◽  
...  
Keyword(s):  
Confidence Interval ◽  
High Performance ◽  
Plasma Concentrations ◽  
Systemic Circulation ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Etoposide Phosphate ◽  
Elimination Half ◽  
Constant Rate

PURPOSE To assess the pharmacokinetics and bioequivalence of etoposide following intravenous (i.v.) administration of etoposide phosphate (Etopophos; Bristol-Myers Squibb, Princeton, NJ), a prodrug of etoposide, and VePesid (Bristol-Myers Squibb). PATIENTS AND METHODS Forty-nine solid tumor patients were randomized to receive Etopophos or VePesid on day 1 of a day-1,3,5 schedule of treatment. The alternate drug was given on day 3 and repeated on day 5. The dose, 150 mg/m2 of etoposide equivalent, was administered by constant rate infusion over 3.5 hours. The plasma concentrations of etoposide phosphate and etoposide were determined using validated high-performance liquid chromatography (HPLC) assays. Pharmacokinetic parameters were calculated by a noncompartmental method. Etopophos was considered to be bioequivalent to VePesid if the 90% confidence limits for the differences in mean maximum concentration (Cmax) and AUCinf of etoposide were contained within 80% to 125% for the long-transformed data. RESULTS Forty-one patients were assessable for pharmacokinetics and bioequivalence assessment. Following i.v. administration, etoposide phosphate was rapidly and extensively converted to etoposide in systemic circulation, resulting in insufficient data to estimate its pharmacokinetics. The mean bioavailability of etoposide from Etopophos, relative to VePesid, was 103% (90% confidence interval, 99% to 106%) based on Cmax, and 107% (90 confidence interval, 105% to 110%) based on area under the concentration versus time curve from zero to infinity (AUCinf) values. Mean terminal elimination half-life (t1/2), steady-state volume of distribution (Vss), and total systemic clearance (CL) values of etoposide were approximately 7 hours, 7 L/m2, and 17 mL/min/m2 after Etopophos and VePesid treatments, respectively. The main toxicity observed was myelosuppression, characterized by leukopenia and neutropenia. CONCLUSION With respect to plasma levels of etoposide, i.v. Etopophos is bioequivalent to i.v. VePesid.

scholarly journals Pharmacokinetics of clarithromycin after single intravenous and intracrop bolus administrations to broiler chickens

2016 ◽  
Vol 4 (1) ◽  
pp. 12 ◽  
Author(s):  
Hanady AwadAllah ◽  
Shaban Awidat ◽  
Abubakr El-Mahmoudy
Keyword(s):  
Plasma Concentration ◽  
Half Life ◽  
Broiler Chickens ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Plasma Concentrations ◽  
Pharmacokinetic Profile ◽  
Volume Of Distribution ◽  
Bolus Administration ◽  
Systemic Bioavailability

<p>The pharmacokinetics of clarithromycin at a dose of 7.5 mg/kg body weight was evaluated after single intravenous (i.v.) and intracrop (i.c.) bolus administrations in broilers. An HPLC assay using pure clarithromycin base as a standard was used to measure its concentrations in plasma. Following an i.v. bolus injection, the plasma concentration-time curves of clarithromycin were best represented by two-compartment open models. The drug was rapidly distributed and moderately eliminated with half-lives of distribution (<em>t</em><sub>1/2α</sub>) and elimination (<em>t</em><sub>1/2β</sub>) of 0.38 and 4.58 h, respectively. The volume of distribution was large with (V<sub>dss</sub>) value of 6.89 L. The total body clearance (<em>Cl</em><sub>B</sub>) was 1.2 L/h. After i.c. bolus administration of the same dose, clarithromycin was moderately absorbed in broilers with an intermediate absorption half-life (<em>T</em><sub>½ab</sub>) of 0.72 h with peak plasma concentration (<em>C</em><sub>max</sub>) of 1.69 μg/ml attained at 1.7 h (<em>T</em><sub>max</sub>) and systemic bioavailability of 66.54%. The elimination half-life following i.c. administration was 2.11 h. The extent of plasma protein binding percent was 52%. The study recommends the use of clarithromycin in broilers because of its good pharmacokinetic profile indicated by good absorption, bioavailability and plasma concentrations ≥ MICs of many sensitive microorganisms.</p>

scholarly journals Comparison of Plasma, Epithelial Lining Fluid, and Alveolar Macrophage Concentrations of Solithromycin (CEM-101) in Healthy Adult Subjects

2012 ◽  
Vol 56 (10) ◽  
pp. 5076-5081 ◽  
Author(s):  
Keith A. Rodvold ◽  
Mark H. Gotfried ◽  
J. Gordon Still ◽  
Kay Clark ◽  
Prabhavathi Fernandes
Keyword(s):  
Steady State ◽  
High Performance ◽  
Healthy Adult ◽  
Plasma Concentrations ◽  
Epithelial Lining ◽  
Time Curve ◽  
Epithelial Lining Fluid ◽  
Once Daily ◽  
Drug Concentrations ◽  
The Mean

ABSTRACTThe steady-state concentrations of solithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained from intrapulmonary samples during bronchoscopy and bronchoalveolar lavage (BAL) in 30 healthy adult subjects. Subjects received oral solithromycin at 400 mg once daily for five consecutive days. Bronchoscopy and BAL were carried out once in each subject at either 3, 6, 9, 12, or 24 h after the last administered dose of solithromycin. Drug concentrations in plasma, ELF, and AM were assayed by a high-performance liquid chromatography-tandem mass spectrometry method. Solithromycin was concentrated extensively in ELF (range of mean [± standard deviation] concentrations, 1.02 ± 0.83 to 7.58 ± 6.69 mg/liter) and AM (25.9 ± 20.3 to 101.7 ± 52.6 mg/liter) in comparison with simultaneous plasma concentrations (0.086 ± 0.070 to 0.730 ± 0.692 mg/liter). The values for the area under the concentration-time curve from 0 to 24 h (AUC0–24values) based on mean and median ELF concentrations were 80.3 and 63.2 mg · h/liter, respectively. The ratio of ELF to plasma concentrations based on the mean and median AUC0–24values were 10.3 and 10.0, respectively. The AUC0–24values based on mean and median concentrations in AM were 1,498 and 1,282 mg · h/L, respectively. The ratio of AM to plasma concentrations based on the mean and median AUC0–24values were 193 and 202, respectively. Once-daily oral dosing of solithromycin at 400 mg produced steady-state concentrations that were significantly (P< 0.05) higher in ELF (2.4 to 28.6 times) and AM (44 to 515 times) than simultaneous plasma concentrations throughout the 24-h period after 5 days of solithromycin administration.

scholarly journals Population Pharmacokinetics of Vincristine Related to Infusion Duration and Peripheral Neuropathy in Pediatric Oncology Patients

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1789 ◽  
Author(s):  
Mirjam Esther van de Velde ◽  
John Carl. Panetta ◽  
Abraham J. Wilhelm ◽  
Marleen H. van den Berg ◽  
Inge M. van der Sluis ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Population Pharmacokinetics ◽  
Pediatric Oncology ◽  
High Performance ◽  
Peripheral Compartment ◽  
Time Curve ◽  
Mixed Effect ◽  
Liquid Chromatography Tandem Mass ◽  
Post Hoc ◽  
Intercompartmental Clearance

Vincristine (VCR) is frequently used in pediatric oncology and can be administered intravenously through push injections or 1 h infusions. The effects of administration duration on population pharmacokinetics (PK) are unknown. We described PK differences related to administration duration and the relation between PK and VCR-induced peripheral neuropathy (VIPN). PK was assessed in 1–5 occasions (1–8 samples in 24 h per occasion). Samples were analyzed using high-performance liquid chromatography/tandem mass spectrometry. Population PK of VCR and its relationship with administration duration was determined using a non-linear mixed effect. We estimated individual post-hoc parameters: area under the concentration time curve (AUC) and maximum concentration (Cmax) in the plasma and peripheral compartment. VIPN was assessed using Common Terminology Criteria for Adverse Events (CTCAE) and the pediatric-modified total neuropathy score (ped-mTNS). Overall, 70 PK assessments in 35 children were evaluated. The population estimated that the intercompartmental clearance (IC-Cl), volume of the peripheral compartment (V2), and Cmax were significantly higher in the push group. Furthermore, higher IC-Cl was significantly correlated with VIPN development. Administration of VCR by push led to increased IC-Cl, V2, and Cmax, but were similar to AUC, compared to 1 h infusions. Administration of VCR by 1 h infusions led to similar or higher exposure of VCR without increasing VIPN.

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