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, 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 The Role of Pharmacokinetics in Anaesthesia: Application to Intravenous Infusions

1987 ◽  
Vol 15 (1) ◽  
pp. 7-14 ◽  
Author(s):  
D. R. Stanski
Keyword(s):  
Steady State ◽  
Plasma Concentration ◽  
Plasma Concentrations ◽  
Pharmacokinetic Profile ◽  
Volume Of Distribution ◽  
Drug Dose ◽  
Metabolic Clearance ◽  
Drug Infusion ◽  
Fixed Rate ◽  
Elimination Half

Pharmacokinetic concepts describe the relationship between drug dose and resulting plasma concentration. A drug's pharmacokinetic profile can be described by distribution and elimination half-lives, initial volume of distribution, steady-state distribution volume, and metabolic and distributional clearance. After initiating a fixed rate of drug infusion, four to five terminal elimination half-lives are required to reach a steady state of constant plasma concentration. If a loading dose is given, a steady state can be achieved more rapidly. The most rapid method of achieving a constant plasma concentration involves using a variable rate of drug infusion that adjusts for the metabolic clearance and distribution of the drug. Computer-driven infusion pumps can be used to rapidly achieve, then maintain, constant plasma concentrations of a drug.

scholarly journals Pharmacokinetics of Ceftaroline in Normal Body Weight and Obese (Classes I, II, and III) Healthy Adult Subjects

2015 ◽  
Vol 59 (7) ◽  
pp. 3956-3965 ◽  
Author(s):  
Julie Ann Justo ◽  
Stockton M. Mayer ◽  
Manjunath P. Pai ◽  
Melinda M. Soriano ◽  
Larry H. Danziger ◽  
...  
Keyword(s):  
Body Weight ◽  
Healthy Adult ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Total Body Weight ◽  
Pharmacokinetic Profile ◽  
Volume Of Distribution ◽  
Population Pharmacokinetic ◽  
Ceftaroline Fosamil ◽  
Plasma And Urine Samples

ABSTRACTThe pharmacokinetic profile of ceftaroline has not been well characterized in obese adults. The purpose of this study was to evaluate the pharmacokinetics of ceftaroline in 32 healthy adult volunteers aged 18 to 50 years in the normal, overweight, and obese body size ranges. Subjects were evenly assigned to 1 of 4 groups based on their body mass index (BMI) and total body weight (TBW) (ranges, 22.1 to 63.5 kg/m2and 50.1 to 179.5 kg, respectively). Subjects in the lower-TBW groups were matched by age, sex, race/ethnicity, and serum creatinine to the upper-BMI groups. Serial plasma and urine samples were collected over 12 h after the start of the infusion, and the concentrations of ceftaroline fosamil (prodrug), ceftaroline, and ceftaroline M-1 (inactive metabolite) were assayed. Noncompartmental and population pharmacokinetic analyses were used to evaluate the data. The mean plasma ceftaroline maximum concentration and area under the curve were ca. 30% lower in subjects with a BMI of ≥40 kg/m2compared to those <30 kg/m2. A five-compartment pharmacokinetic model with zero-order infusion and first-order elimination optimally described the plasma concentration-time profiles of the prodrug and ceftaroline. Estimated creatinine clearance (eCLCR) and TBW best explained ceftaroline clearance and volume of distribution, respectively. Although lower ceftaroline plasma concentrations were observed in obese subjects, Monte Carlo simulations suggest the probability of target attainment is ≥90% when the MIC is ≤1 μg/ml irrespective of TBW or eCLCR. No dosage adjustment for ceftaroline appears to be necessary based on TBW alone in adults with comparable eCLCR. Confirmation of these findings in infected obese patients is necessary to validate these findings in healthy volunteers. (This study has been registered at ClinicalTrials.gov under registration no. NCT01648127.)

scholarly journals Analgesic and Nonanalgesic Effects of Intravenous Hydromorphone - Relation to Plasma Concentrations in Healthy Volunteers

1996 ◽  
Vol 1 (2) ◽  
pp. 86-92 ◽  
Author(s):  
D Westerling ◽  
H Bjork ◽  
P Svedman ◽  
P Hoglund
Keyword(s):  
Healthy Volunteers ◽  
Analgesic Effect ◽  
High Performance ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Systemic Clearance ◽  
The Third ◽  
Elimination Half ◽  
Pressure Pain Thresholds ◽  
Saliva Production

OBJECTIVE:To investigate the analgesic and nonanalgesic effects and the pharmacokinetics of an intravenous infusion of 2 mg hydromorphone over 20 mins.DESIGN:Open study.SUBJECTS:Twelve healthy volunteers.MEASUREMENTS:The analgesic effect of hydromorphone was evaluated serially using pressure pain thresholds (PPTs) measured on the third fingers and toes. The nonanalgesic effects of hydromorphone were measured as miosis, decrease of saliva production and central nervous effects such as euphoria/dysphoria, nausea, headache, fatigue and feeling of heaviness. Plasma concentration of hydromorphone was measured using high performance liquid chromatography.RESULTS:PPTs were significantly increased compared with baseline levels for up to 2 h after the infusion of hydromorphone. Significant miosis and reduction of saliva production were registered up to 6 h after drug administration. Fatigue and heaviness were reported by all subjects. In the studied opioid-naive subjects, the hydromorphone-induced analgesic effect was of shorter duration than the studied nonanalgesic effects. The terminal elimination half-life of hydromorphone was 1.87±0.4 h (± SD) (95% CI 1.61 to 2.13), systemic clearance was 1.81±0.25 L/min (95% CI 1.65 to 1.97) and volume of distribution was 4.15±0.86 L/kg (95% CI 3.6 to 4.71).CONCLUSION:Analgesia and nonanalgesic effects appear to be well correlated with the plasma concentrations of the hydromorphone.

Pharmacokinetics of Prilocaine after Intravenous Administration in Volunteers 

1999 ◽  
Vol 90 (4) ◽  
pp. 988-992 ◽  
Author(s):  
Auke Dirk van der Meer ◽  
Anton G. L. Burm ◽  
Rudolf Stienstra ◽  
Jack W. van Kleef ◽  
Arie A. Vletter ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
High Performance ◽  
Equilibrium Dialysis ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Unbound Fraction ◽  
Blood Samples ◽  
The Mean ◽  
The Difference

Background Prilocaine exists in two stereoisomeric configurations, the enantiomers S(+)- and R(-)-prilocaine. The drug is clinically used as the racemate. This study examined the pharmacokinetics of the enantiomers after intravenous administration of the racemate. Methods Ten healthy male volunteers received 200 mg racemic prilocaine as a 10-min intravenous infusion. Blood samples were collected for 8 h after the start of the infusion. Plasma concentrations were measured by stereoselective high-performance liquid chromatography (HPLC). Unbound fractions of the enantiomers in blank blood samples, spiked with racemic prilocaine, were determined using equilibrium dialysis. Results The unbound fraction of R(-)-prilocaine (mean +/- SD, 70%+/-8%) was smaller (P &lt; 0.05) than that of S(+)-prilocaine (73%+/-5%). The total plasma clearance of R(-)-prilocaine (2.57+/-0.46 l/min) was larger (P &lt; 0.0001) than that of S(+)-prilocaine (1.91+/-0.30 l/min). The steady-state volume of distribution of R(-)-prilocaine (279+/-94 l) did not differ from that of S(+)-prilocaine (291+/-93 l). The terminal half-life of R(-)-prilocaine (87+/-27 min) was shorter (P &lt; 0.05) than that of S(+)-prilocaine (124+/-64 min), as was the mean residence time of R(-)-prilocaine (108+/-30 min) compared with S(+)-prilocaine (155+/-59 min; P &lt; 0.005). Conclusions The pharmacokinetics of prilocaine are enantioselective. The difference in clearance is most likely a result of a difference in intrinsic metabolic clearance. The difference in the pharmacokinetics of the enantiomers of prilocaine does not seem to be clinically relevant.

scholarly journals Pharmacokinetics of sodium meclofenamate in pre-ruminant cattle

2004 ◽  
Vol 56 (6) ◽  
pp. 695-700
Author(s):  
E.J. Picco ◽  
D.C. Diaz David ◽  
T. Encinas ◽  
M.R. Rubio ◽  
J.C. Boggio
Keyword(s):  
High Performance ◽  
Pharmacokinetic Profile ◽  
Apparent Volume ◽  
Antiinflammatory Drug ◽  
Volume Of Distribution ◽  
Intramuscular Administration ◽  
Flip Flop ◽  
Elimination Phase ◽  
Distribution Phase ◽  
Apparent Volume Of Distribution

The pharmacokinetic profile of sodium meclofenamate, a non-steroidal antiinflammatory drug, was determined in six pre-ruminant calves after intravenous and intramuscular administration at a dose of 2.2mg/kg of body weight. Meclofenamate concentrations were measured using a high performance liquid chromatography assay. The pharmacokinetics of sodium meclofenamate after intravenous and intramuscular administration to calves were characterised by a rapid distribution phase (t½alpha ), 15.45± 4.85min and 23.14± 7.24min for the intravenous and intramuscular administration, respectively, followed by a longer elimination phase (t½beta ) after intramuscular treatment (17.55± 6.52h.). The apparent volume of distribution (Vd) of the drug after intravenous administration was moderate (0.72± 0.12l/kg), and high (3.51± 1.05l/kg) after intramuscular administration. This can be explained by the flip-flop effect or by enterohepatic shunting. The bioavailability achieved after intramuscular administration was 61%.

Pharmacokinetics and metabolism of 4'-iodo-4'-deoxy-doxorubicin in humans.

1992 ◽  
Vol 10 (7) ◽  
pp. 1183-1190 ◽  
Author(s):  
J Robert ◽  
J P Armand ◽  
S Huet ◽  
M Klink-Alakl ◽  
G Recondo ◽  
...  
Keyword(s):  
Blood Cell ◽  
High Performance ◽  
Parent Compound ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Parent Drug ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Hematologic Toxicity ◽  
Cell Counts

PURPOSE 4'-iodo-4'-deoxydoxorubicin is a new anthracycline that currently is under clinical evaluation. To improve the management of future trials, we have determined its pharmacokinetics and metabolism during a phase I/II study and have tried to relate the parameters obtained to the hematologic toxicity of the drug in terms of the survival of blood cells. PATIENTS AND METHODS The pharmacologic study included 19 patients who were entered at dose levels that ranged between 6 and 90 mg/m2; nine patients were treated at 80 mg/m2, which is close to the maximum recommended dose level. Blood sampling was performed from the end of the bolus infusion to 48 hours after treatment. Drug and metabolites were extracted and analyzed by high-performance liquid chromatography (HPLC), and the data were processed by nonlinear fitting to multicompartment models. RESULTS Plasma concentrations were best fitted to a three-compartment model with half-lives of 5.2 minutes, 0.79 hours, and 10.3 hours. The total body clearance and volume of distribution at steady state were high (350 L/h/m2 and 2,065 L/m2). The drug was metabolized extensively to a 13-dihydroderivative, 4'-iodo-4'-deoxy-doxorubicinol; the mean area under the curve (AUC) ratio metabolite/parent drug was the highest observed ever for an anthracycline (12.1 +/- 7.4); the metabolite was cleared from the plasma with an elimination half-life of 15.3 hours. The AUCs of the parent compound and its metabolite were related linearly to the dose administered, and showed no saturation phenomenon. Urinary excretion was studied in nine patients and showed a cumulative elimination of less than 6% of the dose administered, two thirds of which were eliminated in the first 12 hours after injection. Ninety-three percent to 100% of the elimination of fluorescent compounds occurred in the form of the metabolite. Drug concentration in five tumor samples showed a rapid uptake of the drug from plasma and a preferential uptake of the parent drug compared with the metabolite. Blood cell counts after 4'-iodo-4'-deoxydoxorubicin treatment showed significant correlations among the surviving fractions of both granulocytes and platelets and the AUCs of the parent drug and its metabolite; the most significant correlations were obtained for the granulocytes and the metabolite. Significant correlations between AUCs and blood-cell survivals were maintained, even if only the nine patients treated at the dose of 80 mg/m2 were taken into account for the computation. CONCLUSIONS Our results especially show that myelosuppression that is induced by 4'-iodo-4'-deoxydoxorubicin can be well predicted by the measure of the AUC of the drug and its metabolite. This could be used for the further development of the drug toward high-dosage schedules.

Optimization of high-dose busulfan dosing in bone marrow transplant patients

1996 ◽  
Vol 2 (1_suppl) ◽  
pp. 18-26
Author(s):  
James S. Partyka ◽  
Cheryl Tate
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplant ◽  
Plasma Concentrations ◽  
Systemic Exposure ◽  
Pharmacokinetic Profile ◽  
Volume Of Distribution ◽  
Marrow Transplant ◽  
High Dose ◽  
Medline Search ◽  
Transplant Patients

Objective. To review the pharmacokinetics profile of (HD-BU) high-dose busulfan, review published phar macodynamic relationships of high-dose busulfan and discuss clinical considerations of monitoring patients receiving high-dose busulfan. Data Sources. A MEDLINE search of articles published from 1985 to 1996 and a Cancerlit search of articles published from 1988 to 1996, using the Mesh headings "Busulfan (subheading: pharmacokinetics)," "Bone Marrow Transplantation" and "Hepatic Veno occlusive Disease." Study Selection. All human trials evaluating the pharmacokinetic profile and the pharmacodynamic relationships of high-dose busulfan in bone marrow transplant patients. Data Synthesis. Busulfan disposition has been extensively studied in both children and adults receiv ing high doses followed by stem cell rescue. Sample sizes ranged from 7 to 28 patients, with patients ranging from 0.3 to 60 years of age. Busulfan total doses ranged from 14 mg/kg to 640 mg/m2. A large interpatient variability has been reported in busulfan pharmacokinetics parameters for both children and adults. In adults, the maximum concentration (Cmax) achieved after the first oral dose of HD-BU ranged from 249 to 1512 ng/mL, the apparent volume of distribution (Vd) ranged from 0.56 to 0.66 L/kg, the total plasma clearance (CL) of busulfan ranged from 2.49 to 3.26 mL/min/kg, and the area under the time versus concentration curve (AUC) ranged from 103 to 21,120 ng h/mL. In children, the Cmax ranged from 577 to 1258 ng/mL, the Vd ranged from 0.74 to 1.42 L/kg, the CL of busulfan ranged from 3.26 to 8.91 mL/min/kg, and the AUC ranged from 309 to 13,129 ng h/mL. Several investigators have reported in creased busulfan CL, larger Vd and lower Cmax in children as compared to adults. In addition, children have lower AUCs as compared with adults when administered a fixed busulfan dose based on body weight. Lower busulfan AUCs in children appear to be the result of an increased systemic clearance and a larger volume of distribution as compared to adults. In adults, HD-BU systemic exposure have been corre lated to efficacy and toxicity in some studies; no prospective studies in children have established a clear role for routinely monitoring busulfan concen trations. Conclusions. Although routine monitoring with dosage adjustment of busulfan is probably warranted in some patients with extremely high or low busulfan plasma concentrations, clinical studies should con tinue to further define a therapeutic range for HD-BU.

scholarly journals Pharmacokinetics of Tildipirosin in Ewes after Intravenous, Intramuscular and Subcutaneous Administration

Animals ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1332
Author(s):  
Juan Sebastián Galecio ◽  
Elisa Escudero ◽  
José Joaquín Cerón ◽  
Giuseppe Crescenzo ◽  
Pedro Marín
Keyword(s):  
Bacterial Infections ◽  
High Performance ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Subcutaneous Administration ◽  
Apparent Volume ◽  
Wide Distribution ◽  
Volume Of Distribution ◽  
Time Data ◽  
Administration Time

A single-dose disposition kinetics for tildipirosin was evaluated in clinically healthy ewes (n = 6) after intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration of a commercial formulation. Tildipirosin concentrations were determined by high-performance liquid chromatography with ultraviolet detection. Plasma concentration-time data was calculated by non-compartmental pharmacokinetic methods. The apparent volume of distribution (Vz) of tildipirosin after IV administration was 5.36 ± 0.57 L/kg suggesting a wide distribution in tissues and inside the cells. The elimination half-life (t½λz) was 17.16 ± 2.25, 23.90 ± 6.99 and 43.19 ± 5.17 h after IV, IM and SC administration, respectively. Following IM administration, tildipirosin was rapidly absorbed (tmax = 0.62 ± 0.10 h) even to a greater extent than after SC administration. Time to reach peak concentration (tmax) and peak plasma concentrations (Cmax) differed significantly, but both parameters showed a more significant variability after SC than after IM administration. Bioavailabilities after extravascular administration were high (>70%). Therefore, given general adverse reactions that were not observed in any ewe and favourable pharmacokinetics, tildipirosin could be effective in treating bacterial infections in sheep.

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