scholarly journals Effect of polyaspartic acid on pharmacokinetics of gentamicin after single intravenous dose in the dog.

1996 ◽  
Vol 40 (5) ◽  
pp. 1237-1241 ◽  
Author(s):  
T Whittem ◽  
K Parton ◽  
K Turner
Keyword(s):  
Aspartic Acid ◽  
Elimination Rate ◽  
Volume Of Distribution ◽  
Intravenous Dose ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Peripheral Compartment ◽  
Single Intravenous Dose ◽  
Polyaspartic Acid ◽  
Peripheral Tissues

The effects of poly-L-aspartic acid on the pharmacokinetics of gentamicin were examined by using a randomized crossover trial design with the dog. When analyzed according to a three-compartment open model, poly-L-aspartic acid reduced some first-order rate equation constants (A3, lambda 1, and lambda 3), the deep peripheral compartment exit microconstant (k31), the elimination rate constant (k(el)), and the area under the concentration-time curve from 0 to 480 h (AUC0-480) (0.21-, 0.60-, 0.26-, 0.27-, 0.72-, and 0.76-fold, respectively; P < 0.05) but increased the volume of distribution at steady state (Vss), the volume of distribution calculated by the area method (V(area)), the apparent volume of the peripheral compartment (Vp), and all mean time parameters. These results suggested that poly-L-aspartic acid increased the distribution of gentamicin to or binding within the deep peripheral compartment and that poly-L-aspartic acid may have delayed gentamicin transit through the peripheral tissues. In contrast, poly-L-aspartic acid did not alter pharmacokinetic parameters relevant to the central or shallow peripheral compartments to a clinically significant extent. Although gentamicin's pharmacokinetic parameters of relevance to therapeutic drug monitoring were not directly altered, this study has provided pharmacokinetic evidence that poly-L-aspartic acid alters the peripheral distribution of gentamicin. This pharmacokinetic interaction occurred after a single intravenous dose of each drug. Therefore, this interaction should be investigated further, before polyaspartic acid can be considered for use as a clinical nephroprotectant.

scholarly journals Pharmacokinetics of a Fluoronaphthyridone, Trovafloxacin (CP 99,219), in Infants and Children following Administration of a Single Intravenous Dose of Alatrofloxacin

2000 ◽  
Vol 44 (5) ◽  
pp. 1195-1199 ◽  
Author(s):  
John S. Bradley ◽  
Gregory L. Kearns ◽  
Michael D. Reed ◽  
Edmund V. Capparelli ◽  
John Vincent
Keyword(s):  
Volume Of Distribution ◽  
Intravenous Dose ◽  
Pharmacokinetic Parameters ◽  
Single Intravenous Dose ◽  
Average Standard Deviation ◽  
Time Curve ◽  
Concentration Time ◽  
Age Related ◽  
The Mean ◽  
In Infants And Children

ABSTRACT The pharmacokinetics of trovafloxacin following administration of a single intravenous dose of alatrofloxacin, equivalent to 4 mg of trovafloxacin per kg of body weight, were determined in 6 infants (ages 3 to 12 months) and 14 children (ages, 2 to 12 years). There was rapid conversion of alatrofloxacin to trovafloxacin, with an average ± standard deviation (SD) peak trovafloxacin concentration determined at the end of the infusion of 4.3 ± 1.4 μg/ml. The primary pharmacokinetic parameters (average ± SD) analyzed were volume of distribution at steady state (1.6 ± 0.6 liters/kg), clearance (151 ± 82 ml/h/kg), and half-life (9.8 ± 2.9 h). The drug was well tolerated by all children. There were no age-related differences in any of the pharmacokinetic parameters studied. Less than 5% of the administered dose was excreted in the urine over 24 h. On the basis of the mean area under the concentration-time curve of 30.5 ± 10.1 μg · h/ml and the susceptibility (≤0.5 μg/ml) of common pediatric bacterial pathogens to trovafloxacin, dosing of 4 mg/kg/day once or twice daily should be appropriate.

Ketamine kinetics: decerebrate vs. intact cats

1979 ◽  
Vol 57 (8) ◽  
pp. 878-881 ◽  
Author(s):  
James E. Heavner ◽  
Duane C. Bloedow
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
Drug Dose ◽  
The Body ◽  
Pharmacokinetic Parameters ◽  
Peripheral Compartment ◽  
Blood Concentrations ◽  
Open Model ◽  
Apparent Volume Of Distribution ◽  
Compartment Open Model

Pharmacokinetic parameters of a ketamine (10 mg/kg, iv) bolus in decerebrate and intact cats were compared. A two-compartment open model best described the data in both groups. The apparent volume of distribution of the peripheral compartment, the apparent volume of distribution of the drug in the body, and the half-life of the postdistributive phase were significantly less (p < 0.05) in the decerebrate animals. These results emphasize the importance of correlating behavior and neuronal activity with plasma or blood concentrations of drug in animals rather than assuming that, for a given drug dose, blood (and thus tissue) levels of the agent will be similar regardless of how the animal is prepared for study.

Letters to the Editor

PEDIATRICS ◽  
1981 ◽  
Vol 68 (4) ◽  
pp. 601-602
Author(s):  
M. Spino ◽  
J. J. Thiessen ◽  
A. Isles ◽  
H. Levison ◽  
S. M. MacLeod
Keyword(s):  
Clinical Application ◽  
Drug Concentration ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Intravenous Dose ◽  
Single Intravenous Dose ◽  
Letters To The Editor ◽  
Potential Clinical Application ◽  
Apparent Volume Of Distribution

We found the report by Feldman et al1 interesting with potential clinical application. However, we would like to point out an error in their determination of the apparent volume of distribution (V) and comment on both their methodology and results. They state that V was calculated by dividing the dose of the drug by the extrapolated y intercept for drug concentration at time 0. This method is correct for a drug which exhibits monoexponential elimination following a single intravenous dose.

scholarly journals Pharmacokinetics of Intermittent Intravenous Cefazolin and Tobramycin in Patients Treated with Automated Peritoneal Dialysis

2000 ◽  
Vol 11 (7) ◽  
pp. 1310-1316
Author(s):  
HAROLD J. MANLEY ◽  
GEORGE R. BAILIE ◽  
REGINALD FRYE ◽  
LORRAINE D. HESS ◽  
M. DONALD MCGOLDRICK
Keyword(s):  
Peritoneal Dialysis ◽  
Intravenous Administration ◽  
Intraperitoneal Administration ◽  
Intravenous Dose ◽  
Urine Samples ◽  
Pharmacokinetic Parameters ◽  
Single Intravenous Dose ◽  
Automated Peritoneal Dialysis ◽  
Minimum Inhibitory Concentrations ◽  
Monoexponential Model

Abstract. There is increasing use of intermittent dosing of antibiotics to treat peritoneal dialysis (PD)-related peritonitis. The disposition of intravenous cefazolin and tobramycin was studied in automated PD (APD) patients. Ten patients were recruited and received a single intravenous dose of cefazolin (15 mg/kg) and tobramycin (0.6 mg/kg). Blood and dialysate samples were collected at the beginning, middle, and end of dwells 1 to 3 (on cycler), and at the end of dwells 4 to 5 (off cycler) for a 24-h period. Baseline and 24-h urine samples were collected. Pharmacokinetic parameters were calculated using a monoexponential model. Cefazolin and tobramycin half-lives were markedly different on cycler than off cycler (cefazolin on cycler : 10.67 ± 4.66 h ; cefazolin off cycler : 23.09 ± 5.6 h ; P = 0.001 ; tobramycin on cycler : 14.27 ± 4.53 h ; tobramycin off cycler : 68.5 ± 26.47 h ; P < 0.001). Mean serum and dialysate concentrations were above minimum inhibitory concentrations of susceptible organisms throughout the 24-h period for both drugs with intravenous administration. A model was developed to examine serum and dialysate concentrations after intermittent intraperitoneal administration of 15 mg/kg cefazolin and 0.6 mg/kg tobramycin. Model-predicted intraperitoneal cefazolin provides adequate serum and dialysate concentrations for 24 h. Intermittent intraperitoneal tobramycin doses must be 1.5 mg/kg for one exchange during the first day and then given as 0.5 mg/kg thereafter. It is concluded that the current empiric dosing recommendations for PD-related peritonitis may be adequate for cefazolin (15 to 20 mg/kg) ; however, tobramycin doses must be changed to 1.5 mg/kg intraperitoneally on day 1, then to 0.5 mg/kg intraperitoneally thereafter in APD patients.

Evaluation of Intravenous Phenobarbital Pharmacokinetics in Critically Ill Patients With Brain Injury

2022 ◽  
Author(s):  
Seyedeh Sana Khezrnia ◽  
Bita Shahrami ◽  
Mohammad Reza Rouini ◽  
Atabak Najafi ◽  
Hamid Reza Sharifnia ◽  
...  
Keyword(s):  
Brain Injury ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Normal Population ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Uv Detector ◽  
Therapeutic Goals ◽  
The Impact

Phenobarbital is still one of the drugs of choice in managing patients with brain injury in the intensive care unit (ICU). However, the impact of acute physiological changes on phenobarbital pharmacokinetic parameters is not well studied. This study aimed to evaluate the pharmacokinetic parameters of parenteral phenobarbital in critically ill patients with brain injury. Patients with severe traumatic or non-traumatic brain injury at high risk of seizure were included and followed for seven days. All patients initially received phenobarbital as a loading dose of 15 mg/kg over 30-minutes infusion, followed by 2 mg/kg/day divided into three doses. Blood samples were obtained on the first and fourth day of study at 1, 2, 5, 8, and 10 hours after the end of the infusion. Serum concentrations of phenobarbital were measured by high-pressure liquid chromatography (HPLC) with an ultraviolet (UV) detector. Pharmacokinetic parameters, including the volume of distribution (Vd), half-life (t1/2), and the drug clearance (CL), were provided by MonolixSuite 2019R1 software using stochastic approximation expectation-maximization (SAEM) algorithm and compared with previously reported parameters in healthy volunteers. Data from seventeen patients were analyzed. The mean value±standard deviation of pharmacokinetic parameters was calculated as follows: Vd: 0.81±0.15 L/kg; t1/2: 6.16±2.66 days; CL: 4.23±1.51 ml/kg/h. CL and Vd were significantly lower and higher than the normal population with the value of 5.6 ml/kg/h (P=0.002) and 0.7 L/kg (P=0.01), respectively. Pharmacokinetic behavior of phenobarbital may change significantly in critically ill brain-injured patients. This study affirms the value of early phenobarbital therapeutic drug monitoring (TDM) to achieve therapeutic goals.

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 Poly(d,l-Lactide-Coglycolide) Particles Containing Gentamicin: Pharmacokinetics and Pharmacodynamics in Brucella melitensis- Infected Mice

2007 ◽  
Vol 51 (4) ◽  
pp. 1185-1190 ◽  
Author(s):  
M. C. Lecaroz ◽  
M. J. Blanco-Prieto ◽  
M. A. Campanero ◽  
H. Salman ◽  
C. Gamazo
Keyword(s):  
Drug Delivery Systems ◽  
Brucella Melitensis ◽  
Free Drug ◽  
Intravenous Dose ◽  
Pharmacokinetic Parameters ◽  
Single Intravenous Dose ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Phagocytic Cells ◽  
Target Organs ◽  
Parameter Values

ABSTRACT Drug delivery systems containing gentamicin were studied as a treatment against experimental brucellosis in mice. Micro- and nanoparticles prepared by using poly(d,l-lactide-coglycolide) (PLGA) 502H and microparticles made of PLGA 75:25H were successfully delivered to the liver and the spleen, the target organs for Brucella melitensis. Both polymers have the same molecular weight but have different lactic acid/glycolic acid ratios. Microparticles of PLGA 502H and 75:25H released their contents in a sustained manner, in contrast to PLGA 502H nanoparticles, which were degraded almost completely during the first week postadministration. The values of the pharmacokinetic parameters after administration of a single intravenous dose of 1.5 mg/kg of body weight of loaded gentamicin revealed higher areas under the curve (AUCs) for the liver and the spleen and increased mean retention times (MRTs) compared to those for the free drug, indicating the successful uptake by phagocytic cells in both organs and the controlled release of the antibiotic. Both gentamicin-loaded PLGA 502H and 75:25H microparticles presented similar pharmacokinetic parameter values for the liver, but those made of PLGA 75:25 H were more effective in targeting the antibiotic to the spleen (higher AUCs and MRTs). The administration of three doses of 1.5 mg/kg significantly reduced the load associated with the splenic B. melitensis infection. Thus, the formulation made with the 75:25H polymer was more effective than that made with 502H microspheres (1.45-log and 0.45-log reductions, respectively, at 3 weeks posttreatment). Therefore, both, pharmacokinetic and pharmacodynamic parameters showed the suitability of 75:25H microspheres to reduce the infection of experimentally infected mice with B. melitensis.

scholarly journals Pregnancy-Related Effects on Lamivudine Pharmacokinetics in a Population Study with 228 Women

2011 ◽  
Vol 56 (2) ◽  
pp. 776-782 ◽  
Author(s):  
Sihem Benaboud ◽  
Jean Marc Tréluyer ◽  
Saik Urien ◽  
Stéphane Blanche ◽  
Naim Bouazza ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Pregnant Women ◽  
Rate Constant ◽  
Clearance Rate ◽  
Placental Transfer ◽  
Elimination Rate ◽  
Volume Of Distribution ◽  
Therapeutic Drug ◽  
Parameter Estimates ◽  
Population Parameter

ABSTRACTThe aim of this study was to describe lamivudine (3TC) pharmacokinetics (PK) in HIV-infected nonpregnant and pregnant women and their fetuses. Samples were collected according to therapeutic drug monitoring from 228 women treated with lamivudine and retrospectively analyzed by a population approach. The samples were also collected from cord blood and amniotic fluid at birth. Lamivudine pharmacokinetics were ascribed to an open two-compartment model with linear absorption and elimination. Mean population parameter estimates (intersubject variability) for women were an absorption rate constant of 1.04 h−1, an elimination clearance rate of 23.6 (0.266) liters · h−1, a central volume of distribution of 109 (0.897) liters, an intercompartmental clearance rate of 6.7 liters/h, and a peripheral volume of distribution of 129 liters. A fetal compartment was linked to maternal circulation by mother-to-cord (or fetus) and cord-to-mother rate constants of 0.463 h−1and 0.538 h−1, respectively. The amniotic fluid compartment was connected to the fetal compartment with an elimination rate constant of 0.163 h−1and a fixed-constant swallowing flow. The placental transfer expressed as fetal-to-maternal area under the concentration-time curve (AUC) ratio was 0.86, and the lamivudine amniotic fluid accumulation, expressed as the amniotic fluid-to-fetal AUC ratio, was 2.9. Pregnant women had a 22% higher apparent clearance than nonpregnant and parturient women; however, this increase did not lead to subexposure and should not require a dosage adjustment.

scholarly journals Extended Interval Tobramycin Pharmacokinetics in a Pediatric Patient With Primary Ciliary Dyskinesia Presenting With an Acute Respiratory Exacerbation

2018 ◽  
Vol 23 (2) ◽  
pp. 159-163
Author(s):  
Kristi L. Higgins ◽  
Cady Noda ◽  
Jeremy S. Stultz
Keyword(s):  
Cystic Fibrosis ◽  
Primary Ciliary Dyskinesia ◽  
Elimination Rate ◽  
Area Under The Curve ◽  
Volume Of Distribution ◽  
Treatment Recommendation ◽  
Pharmacokinetic Parameters ◽  
Maximum Serum ◽  
First Case ◽  
Ciliary Dyskinesia

The pharmacokinetics of tobramycin in patients with ciliary dyskinesia have not been previously reported. A 10-year-old female patient with primary ciliary dyskinesia was admitted to the general pediatrics floor with an acute respiratory exacerbation after several months of worsening lung function that was unresponsive to oral antibiotics. Extrapolating from cystic fibrosis dosing regimens, she was given intravenous tobramycin 320 mg (10.3 mg/kg/day) on admission as a result of concern for a Pseudomonas aeruginosa infection. Two-point pharmacokinetic monitoring revealed a maximum serum concentration (Cmax) of 18.9 mg/L and a 24-hour area under the curve (AUC0–24hr) of 58.8 (mg × hr)/L, as well as a volume of distribution (Vd) of 0.5 L/kg and an elimination rate (Ke) of 0.34 hr−1. After a dosage increase to tobramycin 400 mg (12.8 mg/kg/day), pharmacokinetic parameters on 2 assessments were as follows: Vd 0.37 to 0.39 L/kg, Ke 0.33 to 0.39 hr−1, Cmax 27.8 to 28.7 mg/L, and AUC0–24h 78.4 to 89.4 (mg × hr)/L. This was the first case report of aminoglycoside pharmacokinetics in a patient with ciliary dyskinesia. The administration of larger doses (up to 12.8 mg/kg/day) of extended-interval tobramycin, similar to the treatment recommendation of at least 10 mg/kg/day for cystic fibrosis patients, was necessary in this patient to achieve serum concentrations that were appropriate for treatment.

Prediction of Plasma Drug Concentration Profiles and Pharmacokinetic Parameters of Nifedipine Commercial Tablets using the Convolution Method

2021 ◽  
pp. 5380-5384
Author(s):  
Hamzah Maswadeh ◽  
Ahmed A. H. Abdellatif ◽  
A. Amin Mohammed ◽  
Aiman Y. Alwadi ◽  
A. Ibrahim Mohamed
Keyword(s):  
Drug Concentration ◽  
Elimination Rate ◽  
Volume Of Distribution ◽  
Plasma Drug Concentration ◽  
Pharmacokinetic Parameters ◽  
Concentration Profiles ◽  
Plasma Drug ◽  
First Order ◽  
Convolution Method

The aim of this study was to predict the blood/plasma drug concentration profiles for five brand of nifedipine present on the Saudi Arabia market by using the numerical convolution method and to estimate the pharmacokinetic parameters (Cmax, Tmax, Ka, K and Vd) by the application of the residual method to the predicted plasma drug concentration profiles. Results showed that the higher Cmax was 118.95ng/ml for brand A2 and the lower Cmax was 72.29ng/ml for brand A3. The Tmax was ranged from 2.3 hr to 4.9 hr for brands A2 and A3 respectively. The total area under plasma drug concentration curve (AUCinf.) was in lower value equal to 585.59 ng x hr/ml for brand A2 and the higher value was for brand A5 equal to 743.52ng x hr/ml. The volume of distribution was also increased from 52.5 L for free nifidipine to 72 L for brand A1. The predicted first order elimination rate constant was decreased from 0.34 hr-1 for free nifedipine to 0.17 hr-1 for brand A3. The half-life of nifedapine was increased from 2 hours for free drug to 3.93 hours for brand A3. From this study it can be concluded that brands present in the market that shows similarity in accordance to the Dissimilarity factor f1 are not always guaranty that they will be bioequivalent in vivo and vice versa. Also, this study indicates that the method of convolution is a useful tool for prediction of bioequivalence of different brands present on the market.

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