Evaluation of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Intravenous Dose of Miridesap in Healthy Japanese Subjects

2018 ◽  
Vol 8 (5) ◽  
pp. 612-618
Author(s):  
Hiroko Ino ◽  
Yohei Doi ◽  
Lia Liefaard ◽  
Louise Cookson ◽  
Chao Chen ◽  
...  
Keyword(s):  
Intravenous Dose ◽  
Single Intravenous Dose ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Japanese Subjects

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.

Cytopathology of Cardiac Tissue from Daunomycin-Treated Mice

1971 ◽  
Vol 29 ◽  
pp. 550-551
Author(s):  
Robert H. Liss ◽  
Frances A. Cotton
Keyword(s):  
Cardiac Tissue ◽  
Cardiac Toxicity ◽  
Drug Distribution ◽  
Personal Communication ◽  
Intravenous Dose ◽  
Single Intravenous Dose ◽  
Physiologic Saline ◽  
Histopathologic Changes ◽  
Distribution Studies ◽  
Lung And Kidney

Daunomycin, an antibiotic used in the clinical management of acute leukemia, produces a delayed, lethal cardiac toxicity. The lethality is dose and schedule dependent; histopathologic changes induced by the drug have been described in heart, lung, and kidney from hamsters in both single and multiple dose studies. Mice given a single intravenous dose of daunomycin (10 mg/kg) die 6-7 days later. Drug distribution studies indicate that the rodents excrete most of a single dose of the drug as daunomycin and metabolite within 48 hours after dosage (M. A. Asbell, personal communication).Myocardium from the ventricles of 6 moribund BDF1 mice which had received a single intravenous dose of daunomycin (10 mg/kg), and from controls dosed with physiologic saline, was fixed in glutaraldehyde and prepared for electron microscopy.

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, Safety, and Tolerability of a Single 500-mg or 1000-mg Intravenous Dose of Dalbavancin in Healthy Japanese Subjects

2015 ◽  
Vol 35 (12) ◽  
pp. 785-793 ◽  
Author(s):  
Patrick J. Scoble ◽  
Robert C. Owens ◽  
Sailaja Puttagunta ◽  
Mark Yen ◽  
Michael W. Dunne
Keyword(s):  
Intravenous Dose ◽  
Japanese Subjects

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.

A double-blind trial of a single intravenous dose of metronidazole as prophylaxis against wound infection following appendicectomy

1979 ◽  
Vol 66 (6) ◽  
pp. 428-429 ◽  
Author(s):  
M. J. Greenall ◽  
A. Bakran ◽  
I. R. Pickford ◽  
J. A. Bradley ◽  
A. Halsall ◽  
...  
Keyword(s):  
Wound Infection ◽  
Intravenous Dose ◽  
Double Blind Trial ◽  
Single Intravenous Dose ◽  
Double Blind ◽  
Blind Trial

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.

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