Drug Pharmacokinetics Following a Single IV Bolus Administration: Drug Distribution

2012 ◽  
pp. 58-73
Keyword(s):  
Drug Distribution ◽  
Bolus Administration ◽  
Drug Pharmacokinetics

Effect of Epidural Infusion Bolus Delivery Rate on the Duration of Labor Analgesia

2018 ◽  
Vol 128 (4) ◽  
pp. 745-753 ◽  
Author(s):  
Elizabeth M. S. Lange ◽  
Cynthia A. Wong ◽  
Paul C. Fitzgerald ◽  
Wilmer F. Davila ◽  
Suman Rao ◽  
...  
Keyword(s):  
Breakthrough Pain ◽  
Controlled Trial ◽  
Drug Distribution ◽  
Labor Analgesia ◽  
High Rate ◽  
Bolus Administration ◽  
Singleton Pregnancy ◽  
Double Blind ◽  
Neuraxial Analgesia ◽  
Nulliparous Women

Abstract Background Programmed intermittent boluses of local anesthetic have been shown to be superior to continuous infusions for maintenance of labor analgesia. High-rate epidural boluses increase delivery pressure at the catheter orifice and may improve drug distribution in the epidural space. We hypothesized that high-rate drug delivery would improve labor analgesia and reduce the requirement for provider-administered supplemental boluses for breakthrough pain. Methods Nulliparous women with a singleton pregnancy at a cervical dilation of less than or equal to 5 cm at request for neuraxial analgesia were eligible for this superiority-design, double-blind, randomized controlled trial. Neuraxial analgesia was initiated with intrathecal fentanyl 25 μg. The maintenance epidural solution was bupivacaine 0.625 mg/ml with fentanyl 1.95 μg/ml. Programmed (every 60 min) intermittent boluses (10 ml) and patient controlled bolus (5 ml bolus, lockout interval: 10 min) were administered at a rate of 100 ml/h (low-rate) or 300 ml/h (high-rate). The primary outcome was percentage of patients requiring provider-administered supplemental bolus analgesia. Results One hundred eight women were randomized to the low- and 102 to the high-rate group. Provider-administered supplemental bolus doses were requested by 44 of 108 (40.7%) in the low- and 37 of 102 (36.3%) in the high-rate group (difference –4.4%; 95% CI of the difference, –18.5 to 9.1%; P = 0.67). Patient requested/delivered epidural bolus ratio and the hourly bupivacaine consumption were not different between groups. No subject had an adverse event. Conclusions Labor analgesia quality, assessed by need for provider- and patient-administered supplemental analgesia and hourly bupivacaine consumption was not improved by high-rate epidural bolus administration.

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.

Replacement of oxytocin bolus administration by infusion: influences on adverse postpartum outcome

2014 ◽  
Vol 74 (S 01) ◽  
Author(s):  
JJ Löytved-Hardegg ◽  
M Brunner ◽  
JJ Ries ◽  
S von Felten ◽  
C Heugel ◽  
...  
Keyword(s):  
Bolus Administration

Fibrin-specificity of a Plasminogen Activator Affects the Efficiency of Fibrinolysis and Responsiveness to Ultrasound: Comparison of Nine Plasminogen Activators In Vitro

1999 ◽  
Vol 81 (04) ◽  
pp. 605-612 ◽  
Author(s):  
Dmitry V. Sakharov ◽  
Marrie Barrett-Bergshoeff ◽  
Rob T. Hekkenberg ◽  
Dingeman C. Rijken
Keyword(s):  
Thrombolytic Therapy ◽  
Plasminogen Activator ◽  
Tissue Type ◽  
Bolus Administration ◽  
High Frequency Ultrasound ◽  
Single Chain ◽  
Response Curves ◽  
Maximal Speed ◽  
Frequency Ultrasound

SummaryIn a number of cases, thrombolytic therapy fails to re-open occluded blood vessels, possibly due to the occurrence of thrombi resistant to lysis. We investigated in vitro how the lysis of hardly lysable model thrombi depends on the choice of the plasminogen activator (PA) and is accelerated by ultrasonic irradiation. Lysis of compacted crosslinked human plasma clots was measured after addition of nine different PAs to the surrounding plasma and the effect of 3 MHz ultrasound on the speed of lysis was assessed.Fibrin-specific PAs showed bell-shaped dose-response curves of varying width and height. PAs with improved fibrin-specificity (staphylokinase, the TNK variant of tissue-type PA [tPA], and the PA from the saliva of the Desmodus rotundus bat) induced rapid lysis in concentration ranges (80-, 260-, and 3,500-fold ranges, respectively) much wider than that for tPA (a 35-fold range). However, in terms of speed of lysis, these three PAs exceeded tPA only slightly. Reteplase and single-chain urokinase were comparable to tPA, whereas two-chain urokinase, anistreplase, and streptokinase were inferior to tPA. In the case of fibrin-specific PAs, ultrasonic treatment accelerated lysis about 1.5-fold. For streptokinase no acceleration was observed. The effect of ultrasound correlated with the presence of plasminogen in the outer plasma, suggesting that it was mediated by facilitating the transport of plasminogen to the surface of the clot.In conclusion, PAs with improved fibrin-specificity induce rapid lysis of plasminogen-poor compacted plasma clots in much wider concentration ranges than tPA. This offers a possibility of using single-or double-bolus administration regimens for such PAs. However, it is not likely that administration of these PAs will directly cause a dramatic increase in the rate of re-opening of the occluded arteries since they are only moderately superior to tPA in terms of maximal speed of lysis. Application of high-frequency ultrasound as an adjunct to thrombolytic therapy may increase the treatment efficiency, particularly in conjunction with fibrin-specific PAs.

Combination of Antibiotic Treatment with the Thrombin Inhibitor Recombinant Hirudin for the Therapy of Experimental Klebsiella pneumoniae Sepsis

1994 ◽  
Vol 71 (06) ◽  
pp. 768-772 ◽  
Author(s):  
Gerhard Dickneite ◽  
Jörg Czech
Keyword(s):  
Septic Shock ◽  
Klebsiella Pneumoniae ◽  
Organ Failure ◽  
Therapeutic Effect ◽  
Disseminated Intravascular Coagulation ◽  
Post Infection ◽  
Thrombin Inhibitor ◽  
Bolus Administration ◽  
Bacterial Burden ◽  
Recombinant Hirudin

SummaryRats which were infected with the gramnegative pathogen Klebsiella pneumoniae develop disseminated intravascular coagulation (DIC), multi-organ failure (MOF) and finally die in a septic shock. We investigated the therapeutic effect of antibiotic (tobramycin) treatment combined with the infusion of the highly specific thrombin inhibitor rec. hirudin. Although administration of 2 mg/kg tobramycin alone leads to a decrease of the bacterial burden, DIC could not be prevented. Infusion of rec. hirudin (0.25 mg/kg x h) for 4 h (start of treatment 1 h post infection), in addition to a bolus administration of tobramycin, led to an amelioration of DIC parameters as fibrinogen, thrombin-antithrombin complex (TAT) and platelets. Serum transaminase levels (GOT, GPT) as a marker of MOF were significantly improved by rec. hirudin, the T50 value increased from 17 h in the tobramycin group to 42 h in the tobramycin + rec. hirudin giuup, muilality rates were 90% or 60%, respectively. Combination of heparin (10011/kg x h) and tobramycin was not effective on survival.

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