scholarly journals Studies on effects of lactose on experimental Trypanosoma vivax infection in Zebu cattle. 1. Plasma kinetics of intravenously administered lactose at onset of infection and pathology

2008 ◽  
Vol 75 (2) ◽  
Author(s):  
M. Y. Fatihu ◽  
S. Adamu ◽  
I. A. Umar ◽  
N. D.G. Ibrahim ◽  
L. O. Eduvie ◽  
...  
Keyword(s):  
Muscular Atrophy ◽  
Elimination Rate ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Zebu Cattle ◽  
Trypanosoma Vivax ◽  
Histopathological Lesions ◽  
The Mean ◽  
Total Body

Lactose in normal saline was administered intravenously to a group of Zebu cattle infected with Trypanosoma vivax to determine the bloodplasma kinetics at onset of an experimental infection and its ability to protect tissues against damage as part of preliminary studies to determine its suitability for use in the treatment of trypanosomosis. Significant (P <0.01) higher lactose concentrations were observed in the T. vivax-intecled bulls at 30 min and 1h (P< 0.05) post-infectio (p.i.) and by 4 h p.i. the plasma lactose remained above the level prior to infusion, after which it fell slightly below the preinfusion level in the uninfected group. Calculated pharmacokinetic parameters revealed delayed excretion of lactose in the T. vivax-intected group soon after infection. The total body clearance (C/B )was significantly (P < 0.05) reduced. The biological half-life (t1/2), elimination rate constant (kel) and apparent volume of distribution (Vd) were relatively decreased (P > 0.05) as a result of the T. vivax infection. Retention of lactose in the plasma was attributed to decreased plasma clearance l.t is suggested that the presence of trypanosomes in circulation rather than organic lesions could have been responsible for the delay observed in the excretion of lactose.At 12 weeks p.i., when the experiment was terminated, the group infected and given lactose infusion (despiteh igherp arasitaemia) had no gross or histopathological lesions in the brain, spleen, lymphnodes, heart, kidneys, liver and testes. However, the group infected but not infused with lactose were emaciated, had pale mucosae, watery blood, general muscular atrophy, serous atrophy of coronary fat and other adiposet issue, hepatomegalys, plenomegalys, wollen and oedematous lymph nodes, all of which are suggestive of trypanosomosis. Histopathological lesions included arrowing of Bowman's space and hypercellularity of glomerular tufts in the kidneys with the mean glomerula truft nucleairn dices (GTNs) in the group significantly higher (P <0.01)than the mean GTNs of the lactoseinfused and control bulls. Degenerative changes occurred in the myocardium, spleen, testes and epididymides. The tesicular and epididymal lesions are indicative of male reproductive dysfunction.

scholarly journals Pharmacokinetics of Intravenous Piperacillin Administration in Patients Undergoing On-Line Hemodiafiltration

2009 ◽  
Vol 53 (8) ◽  
pp. 3266-3268 ◽  
Author(s):  
Kook-Hwan Oh ◽  
Chiweon Kim ◽  
Hankyu Lee ◽  
Hajeong Lee ◽  
Ji Yong Jung ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Total Body Clearance ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Recovery Method ◽  
Elimination Half ◽  
On Line ◽  
The Mean ◽  
Total Body ◽  
Body Clearance

ABSTRACT The pharmacokinetic characteristics of piperacillin sodium were studied in five volunteers undergoing on-line hemodiafiltration (HDF). The subjects were given 2 g of piperacillin sodium intravenously over 1 min and placed on on-line HDF for 4 h starting at 60 min after the piperacillin infusion. Noncompartmental models were employed for estimation of the pharmacokinetic parameters, and intradialytic piperacillin clearance was calculated by the recovery method. The mean volume of distribution and the elimination half-life were 0.27 ± 0.13 liter/kg (mean ± standard deviation) and 1.1 ± 0.6 h, respectively. The total body clearance of piperacillin was 0.19 ± 0.08 liter/h/kg. Piperacillin clearance through on-line HDF was 0.11 ± 0.06 liter/h/kg. The mean serum piperacillin concentration was 4.0 ± 1.9 μg/ml at the end of the 4-h on-line HDF session. The concentration of infused piperacillin recovered in the dialysate was 527 ± 236 mg (26.3% ± 11.8%). We suggest the replacement of 500 mg of piperacillin after each on-line HDF session.

scholarly journals Compartmental Pharmacokinetics of the Antifungal Echinocandin Caspofungin (MK-0991) in Rabbits

2001 ◽  
Vol 45 (2) ◽  
pp. 596-600 ◽  
Author(s):  
Andreas H. Groll ◽  
Bryan M. Gullick ◽  
Ruta Petraitiene ◽  
Vidmantas Petraitis ◽  
Myrna Candelario ◽  
...  
Keyword(s):  
High Performance ◽  
Pharmacokinetic Model ◽  
Area Under The Curve ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Chromatography Method ◽  
Opportunistic Fungi ◽  
The Mean ◽  
Liquid Chromatography Method

ABSTRACT The pharmacokinetics of the antifungal echinocandin-lipopeptide caspofungin (MK-0991) in plasma were studied in groups of three healthy rabbits after single and multiple daily intravenous administration of doses of 1, 3, and 6 mg/kg of body weight. Concentrations were measured by a validated high-performance liquid chromatography method and fitted into a three-compartment open pharmacokinetic model. Across the investigated dosage range, caspofungin displayed dose-independent pharmacokinetics. Following administration over 7 days, the mean peak concentration in plasma (C max) ± standard error of the mean increased from 16.01 ± 0.61 μg/ml at the 1-mg/kg dose to 105.52 ± 8.92 μg/ml at the 6-mg/kg dose; the mean area under the curve from 0 h to infinity rose from 13.15 ± 2.37 to 158.43 ± 15.58 μg · h/ml, respectively. The mean apparent volume of distribution at steady state (Vdss) was 0.299 ± 0.011 liter/kg at the 1-mg/kg dose and 0.351 ± 0.016 liter/kg at the 6-mg/kg dose (not significant [NS]). Clearance (CL) ranged from 0.086 ± 0.017 liter/kg/h at the 1-mg/kg dose to 0.043 ± 0.004 liter/kg/h at the 6-mg/kg dose (NS), and the mean terminal half-life was between 30 and 34 h (NS). Except for a trend towards an increasedVdss, there were no significant differences in pharmacokinetic parameters in comparison to those after single-dose administration. Caspofungin was well tolerated, displayed linear pharmacokinetics that fit into a three-compartment pharmacokinetic model, and achieved sustained concentrations in plasma that were multiple times in excess of reported MICs for susceptible opportunistic fungi.

scholarly journals Plasma pharmacokinetics of ciprofloxacin in sheep

1970 ◽  
Vol 6 (1) ◽  
pp. 93-97
Author(s):  
MS Islam ◽  
MMH Sikder ◽  
MA Awal ◽  
M Mostofa ◽  
AA Trisha
Keyword(s):  
Half Life ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Sheep Model ◽  
First Order Kinetics ◽  
Healthy Sheep ◽  
Plasma Pharmacokinetics ◽  
Total Body

The study was carried out to determine the biodisposition kinetics of ciprofloxacin in sheep model in Department of Pharmacology, Bangladesh Agricultural University. Healthy sheep of both sexes (n=65) were divided into 13 groups, each consists of five and given a single dose of ciprofloxacin @ 5 mg/kg bwt intramuscularly .Blood sample was collected from each group of sheep at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10 and 12 hours interval respectively. Serum concentration of ciprofloxacin was determined by spectrophotometric method. The pharmacokinetic parameters were measured by single compartment open model and first order kinetics. The peak concentration of ciprofloxacin was 3.56±0.15mg/ ml, absorption half-life and biological half-life were 0.0846±1.79 and 1.75±0.15 h respectively. The apparent volume of distribution was found 35.54 mg/liter. The absorption rate constant was 8.188h-1, MRT was 2.647h-1 and total body clearances were found 16.88 h-1. These result suggested that a dose of 5 mg/kg bwt provides maximum plasma concentration and is effective in the control of many infectious diseases of sheep. Key words: Plasma pharmacokinetics, ciprofloxacin, sheep DOI = 10.3329/bjvm.v6i1.1344 Bangl. J. Vet. Med. (2008). 6 (1): 93-97

Gentamicin Pharmacokinetics in Elderly Patients with Normal Renal Function

1994 ◽  
Vol 10 (1) ◽  
pp. 14-17 ◽  
Author(s):  
Ji M. Koo ◽  
Donald R. Miller ◽  
Charles D. Peterson
Keyword(s):  
Renal Function ◽  
Elderly Patients ◽  
Normal Renal Function ◽  
Medical Center ◽  
Elimination Rate ◽  
The Elderly ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Trough Concentrations ◽  
The Mean

Objective: To establish the pharmacokinetic parameters of gentamicin in elderly patients and to compare predicted concentrations based on the Dettli method, with actual concentrations. Design: Measurement of gentamicin concentrations and pharmacokinetic parameters in a consecutive patient sample with comparison to ones predicted by the Dettli method. Setting: Medical and surgical units in a Veterans Affairs Medical Center. Patients: Forty-six consecutive elderly men treated with gentamicin for documented or presumed infection and had stable, normal renal function. Main Outcome Measures: The following information was calculated or measured: elimination rate constant (kel), elimination half-life, volume of distribution (Vd), and peak and trough concentrations. Results: The mean kel (0.16 ± 0.05 h−1) was not significantly different (p=0.2) from the Dettli method prediction, and the mean Vd (0.36 ± 0.1 L/kg) was 37 percent higher than that usually reported. Actual peak and trough concentrations were significantly lower (both p<0.01) than predicted concentrations. Conclusions: Based on our findings, higher than recommended loading doses and longer dosage intervals may be required in the elderly. The Dettli method is useful to estimate kel in the elderly.

scholarly journals Evaluation of pharmacokinetics of warfarin from validated pharmacokinetic-pharmacodynamic model

ADMET & DMPK ◽  
2021 ◽  
Author(s):  
Kannan Sridharan ◽  
Rashed Al Banna ◽  
Aysha Husain
Keyword(s):  
Elimination Rate ◽  
Liver Weight ◽  
International Normalized Ratio ◽  
Volume Of Distribution ◽  
Pharmacodynamic Model ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
The Mean ◽  
Study Participants ◽  
The Relationship

Background: Pharmacokinetics of warfarin has not been described in our population. We derived the pharmacokinetic parameters from a validated pharmacokinetic-pharmacodynamic model. Methods: Patients receiving warfarin for at least 6 months were recruited and their demographic characteristics, prothrombin time international normalized ratio (PT-INR), warfarin doses and concomitant drugs were collected. Using a validated pharmacokinetic-pharmacodynamic model, we predicted maximum plasma concentration (Cmax), total clearance (CL), volume of distribution (Vd) and elimination rate (k). Warfarin sensitive index (WSI) and warfarin composite measures (WCM) were estimated from the dose and INR values. Liver weight was predicted using validated formula. Results: Two-hundred and twenty patients were recruited. The following were the predicted pharmacokinetic parameters: Cmax (mg/L) was 5.8 (0.4); k (L/day) was 1 (0.1); CL (L/day) was 2.1 (0.2); and Vd (L) was 7.6 (0.2). Patients with Cmax and elimination rate outside the mean+1.96 SD had significantly lower WSI and higher WCM. Significant correlations were observed between Cmax with CL, Vd, and k of warfarin. Significant correlations were also observed between CL and Vd of warfarin with liver weight of the study participants. Conclusion: We predicted pharmacokinetic parameters of warfarin from the validated pharmacokinetic-pharmacodynamic model in our population. More studies are needed exploring the relationship between various pharmacodynamic indices of warfarin and pharmacokinetic parameters of warfarin.

Pharmacokinetics of PT523, a novel aminopterin analogue, in patients with solid tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2052-2052
Author(s):  
J. G. Supko ◽  
X. He ◽  
N. Sao ◽  
F. D’Amato ◽  
L. Blaszkowsky ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Hepatic Function ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Entire Cohort ◽  
Median Plasma ◽  
Major Route ◽  
The Mean ◽  
Total Body ◽  
Log Linear

2052 Background: Nα-(4-Amino-4-deoxypteroyl)-N5-hemiphthaloyl)-L-ornithine (PT523) is a nonpolyglutamatable aminopterin analogue selected for clinical evaluation based upon properties that confer potential therapeutic advantages over classic and nonclassic antifolates. This report describes the pharmacokinetic (PK) behavior of PT523 in cancer patients as determined in the first phase I trial of the drug. Methods: Adult patients with refractory solid tumors received PT523 as a 5 min iv infusion every 7 days for 3 weeks. Plasma samples were obtained at -5, 4, 10, 15, 20, 30, 45 min; 1, 2, 3, 4, 6, 8, 24, and 48 h after starting the first weekly infusion. Urine was collected and pooled from 0–8, 8–24, and 24–48 h. An LC/MS assay was used to measure PT523 in plasma and urine. Interday accuracy and precision were both <15% at the lowest concentrations measured in plasma (0.50 ng/mL) and urine (50 ng/mL). PK parameters were estimated by standard noncompartmental methods. Results: The PK of PT523 was characterized in 24 patients with normal renal and hepatic function, and a median age of 52 years (range, 28 - 77 years). Data was obtained from groups of at least three patients receiving doses of 5, 6.7, 9, 12, and 16 mg/m2. The PT523 concentration in plasma decreased in a polyexponential manner and the terminal log-linear phase was achieved 4–6 h after dosing. In the 7 patients receiving doses of 16 mg/m2, the mean peak drug concentration in plasma (Cmax) was 5,650 ± 300 ng/mL and the median plasma concentration 48 h after dosing was 1.7 ng/mL (range, 1.0 - 23.4 ng/mL). The apparent biological half-life (t1/2,z), total body clearance (CL) and apparent volume of distribution at steady-state (Vss) were all independent of the dose. Mean ± SD values of PK parameters for the entire cohort of 24 patients were: CL, 1.16 ± 0.31 L/h/m2; t1/2,z, 5.3 ± 1.2 h; Vss, 7.7 ± 1.5 L/m2. The mean amount of the dose excreted as unchanged drug in urine over 48 h was 40 ± 15%. Conclusions: PT523 exhibits linear PK with moderate interpatient variability when administered as a 5 min iv infusion at doses of 5 - 16 mg/m2. Renal clearance is a major route of elimination. Association between the CL of PT523 and creatinine clearance should be evaluated in a future study to assess whether dose modification is warranted for patients with diminished renal function. No significant financial relationships to disclose.

Estimation of Pharmacokinetic Parameters at Steady-State in Patients

1978 ◽  
Vol 12 (10) ◽  
pp. 612-616 ◽  
Author(s):  
James W. Crow ◽  
Milo Gibaldi
Keyword(s):  
Steady State ◽  
Rate Constant ◽  
Elimination Rate ◽  
Simulated Data ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Total Clearance ◽  
Dosing Intervals ◽  
Apparent Volume Of Distribution

A method to characterize the pharmacokinetics of a drug in a patient receiving it chronically is proposed. In principle, such characterization may be carried out by obtaining one or more drug concentration in plasma-time values from several different dosing intervals, combining the data to create a composite dosing interval representative of the steady-state situation and fitting the data to an appropriate equation. The method was evaluated using simulated data based on the average pharmacokinetic parameters of theophylline in children. Reasonable estimates of the elimination rate constant and apparent volume of distribution may be obtained, but the estimation of the absorption rate constant presents formidable problems. The method appears to be most useful for obtaining very accurate estimates of total clearance.

Gentamicin and Tobramycin Pharmacokinetics in Pediatric Bone Marrow Transplant Patients

1997 ◽  
Vol 31 (10) ◽  
pp. 1127-1131 ◽  
Author(s):  
Pamala A Jacobson ◽  
Nina J West ◽  
Jessica Price ◽  
Raymond J Hutchinson
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplant ◽  
Elimination Rate ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Marrow Transplant ◽  
University Teaching ◽  
Pharmacokinetic Parameters ◽  
Marrow Graft ◽  
Transplant Patients

OBJECTIVE: To describe the pharmacokinetic parameters of gentamicin and tobramycin in pediatric bone marrow transplant patients. DESIGN: Retrospective medical record review. Setting: Pediatric bone marrow transplant unit in a university teaching hospital. MAIN OUTCOME MEASURES: Pharmacokinetic parameters (apparent volume of distribution [Vd] in L/kg, half-life [t1/2] in h, elimination rate constant [ke] in h−1, clearance [Cl] in mL/min/1.73 m2 and mL/min/kg) calculated from serum concentrations. PATIENTS: Thirty-three patients aged 15 years or less who underwent bone marrow transplant and received gentamicin or tobramycin. RESULTS: Mean pharmacokinetic parameters were Vd 0.32 ± 0.07 L/kg, t1/2 2.32 ± 0.65 h, Cl 1.71 ± 0.53 mL/min/kg, and Cl 86.2 ± 24.5 mL/min/1.73 m2. Factors such as disease state, type of marrow graft, gender, or exposure to cyclosporine had no significant effect on pharmacokinetic parameters. Linear regression indicated a weak relationship between serum creatinine (SCr) and Cl in mL/min/kg (r = 0.59), but no relationship was found between SCr and Cl in mL/min/1.73 m2, between age and apparent Vd, or between SCr and apparent Vd. Models for estimating Cl and ke developed by multiple regression were somewhat predictive (r = 0.7). Required calculated maintenance dosages to obtain therapeutic concentrations were 8, 7, and 6 mg/kg/d in children 6 or younger, 7–12, and 13–15 years, respectively. CONCLUSIONS: The mean Cl and apparent Vd for all ages are similar to those reported in pediatric oncology patients who had not undergone marrow transplantation. Children 6 years or younger had lower than expected Cls and larger apparent Vds than did the older children. Dosages estimated to be necessary to achieve therapeutic concentrations were 6–8 mg/kg/d.

scholarly journals Linezolid Pharmacokinetics in Adult Patients with Cystic Fibrosis

2004 ◽  
Vol 48 (1) ◽  
pp. 281-284 ◽  
Author(s):  
John A. Bosso ◽  
Patrick A. Flume ◽  
Susan L. Gray
Keyword(s):  
Cystic Fibrosis ◽  
High Performance ◽  
Elimination Rate ◽  
Blood Chemistry ◽  
Volume Of Distribution ◽  
Adult Patients ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Before And After ◽  
Total Body

ABSTRACT The pharmacokinetics of many drugs are altered in patients with cystic fibrosis (CF), often necessitating different dosage requirements than those used in non-CF patients. The objective of this study was to determine the pharmacokinetics of linezolid, an antibiotic with good activity against gram-positive organisms such as methicillin-resistant Staphylococcus aureus, in patients with CF so that dosage requirements could be established. Twelve adult patients (6 male) ranging in age from 22 to 39 years were studied. A single 600-mg dose was administered intravenously over 0.5 h, and plasma samples were collected at 0 (predose), 0.5, 0.75, 1, 2, 4, 8, and 24 h. Linezolid concentrations were determined with a validated high-performance liquid chromatography assay. Pharmacokinetic parameters were estimated using standard noncompartmental methods. Blood chemistry and hematologic indices were determined before and after the study for safety purposes. All patients completed the study without encountering any adverse reactions. The pharmacokinetic parameters, while variable, with half-lives varying from 1.76 to 8.36 h, were similar to those previously described in other populations. Mean (± standard deviation) values for pharmacokinetic parameters of interest were as follows: elimination rate constant, 0.21 (0.11) h−1; half-life, 4.41 (2.43); volume of distribution at steady state, 0.87 (0.19) liters/kg of body weight; and total body clearance, 0.12 (0.06) liters/h/kg. No patient would have achieved the pharmacodynamic target of an area under the concentration-time curve/MIC ratio of 83 h for pathogens for which the MIC was 4 μg/ml. Patients with inadequate clinical responses to linezolid may require more frequent dosing.

scholarly journals Pharmacokinetics of vancomycin in adult cystic fibrosis patients.

1996 ◽  
Vol 40 (1) ◽  
pp. 186-190 ◽  
Author(s):  
R A Pleasants ◽  
E L Michalets ◽  
D M Williams ◽  
W M Samuelson ◽  
J R Rehm ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Standard Deviation ◽  
Creatinine Clearance ◽  
Total Body Clearance ◽  
Elimination Rate ◽  
Clinical Score ◽  
Pharmacokinetic Parameters ◽  
The Mean ◽  
Total Body ◽  
Body Clearance

Although the depositions of many antibiotics are altered in cystic fibrosis patients, that of vancomycin has not been studied. To assess vancomycin pharmacokinetics, 10 adult cystic fibrosis patients were given a parenteral dose of vancomycin (15 mg/kg) during the first 72 h of hospitalization for acute bronchopulmonary exacerbation. Blood samples were obtained at 0, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 15, and 24 h. The mean (standard deviation) weight, measured creatinine clearance, and Taussig clinical score were 51 (13) kg, 130 (39) ml/min/1.73 m2, and 64 (13), respectively. Multicompartmental pharmacokinetic parameters were best described by a two-compartment model. The mean (standard deviation) volume of distribution, total body clearance, and terminal elimination rate constant were 0.58 (0.15) liter/kg, 91 (19) ml/min/1.73 m2, and 0.123 (0.05) h-1, respectively. These values were consistent with vancomycin pharmacokinetic parameters obtained in previous studies of healthy adult volunteers. Vancomycin dosages predicted by using a two-compartment Bayesian model were approximately 15 mg/kg every 8 to 12 h. There were poor correlations between clinical score or creatinine clearance and any pharmacokinetic parameter (r values of < 0.32). The coefficient of correlation between urine flow rate and total body clearance was 0.7 (P < 0.05). Adult cystic fibrosis patients exhibit a disposition of vancomycin similar to that exhibited by healthy adults, and thus cystic fibrosis does not alter vancomycin pharmacokinetics.

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