LID Study: Plasma lidocaine levels following airway topicalisation for paediatric microlaryngobronchoscopy (MLB)

Background A dose of 5mg/kg lidocaine is considered appropriate for paediatric airway topicalisation. Existing literature suggests younger children are susceptible to toxic lidocaine plasma levels and achieve this at a faster rate. Aims The primary outcome of this study was to ascertain peak plasma lidocaine levels after topicalisation for airway endoscopy. Secondary endpoints included: time to peak lidocaine plasma levels, signs of lidocaine toxicity (restricted to ECG changes or seizures when under anaesthesia) and clinical adverse events of laryngospasm, coughing or desaturation during the procedure. Methods Data was collected prospectively over 18 months at Royal Manchester Children’s Hospital. Children aged 0-8 years undergoing elective diagnostic or therapeutic airway endoscopy were included within the study. Standardised 2% lidocaine was used for airway topicalisation. Dose varied depending upon practitioner usual practice. Venous blood sampling occurred at 5, 10, 15 and 20 minutes post administration and plasma lidocaine levels (ng/ml) analysed. Results A significant relationship exists between higher peak plasma levels and ages <18 months (p=0.00973). Strong linear correlation exists between weight and age for our cohort (r=0.88). Higher peak plasma lidocaine levels occur with total dose volumes between 2 and 3mls of 2% lidocaine local anaesthetic (p=0.03) compared with <2ml total dose volumes. Data suggests a potential relationship of lower weights achieving higher peak plasma levels (p=0.0516). Reduced IQR variation of peak plasma lidocaine levels exists when lidocaine dosing is <5mg/kg. Conclusions Age and total dose volume of topicalised lidocaine have a significant relationship with plasma lidocaine levels. A dose of 5mg/kg topicalised lidocaine for paediatric airway endoscopy is safe and provides good operating conditions. Lower patient weights trend toward higher peak lidocaine plasma concentrations and require further investigation.

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Ibuprofen: Plasma Concentrations in Man

Journal of International Medical Research ◽

10.1177/030006058501300110 ◽

1985 ◽

Vol 13 (1) ◽

pp. 68-73 ◽

Cited By ~ 15

Author(s):

G M E Janssen ◽

J F Venema

Keyword(s):

Side Effects ◽

Crossover Study ◽

Plasma Levels ◽

Healthy Subjects ◽

Peak Plasma ◽

Plasma Concentrations ◽

Repeated Dose ◽

Similar Range ◽

The Mean ◽

Peak Value

The plasma levels of Ibuprofen were measured in five healthy subjects who took 600 mg tablets of Ibuprofen twice daily, three times daily and four times daily in a crossover study. Peak plasma levels were obtained 1 hour after the first dose in all but one subject (slow absorber), the mean peak value being 51·3 μg.ml−1 (range 39·4–63·7 μg.ml−1). After the repeated dose regimens of two, three or four times daily of ibuprofen, the peak levels achieved were in a similar range to those seen after the first dose: Twice daily 39·4–66·4 μg.ml−1 Three times daily 43·6–63·3 μg.ml−1 Four times daily 44·1–58·4 μg.ml−1 There was no evidence of accumulation of the drug and no side-effects occurred during the trial.

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EFFECTS OF PINEALECTOMY ON THE SECRETION OF LUTEINIZING HORMONE, TESTOSTERONE AND PROLACTIN IN RAMS EXPOSED TO VARIOUS LIGHTING RÉGIMES

Journal of Endocrinology ◽

10.1677/joe.0.0800397 ◽

1979 ◽

Vol 80 (3) ◽

pp. 397-405 ◽

Cited By ~ 29

Author(s):

G. K. BARRELL ◽

K. R. LAPWOOD

Keyword(s):

Luteinizing Hormone ◽

Pineal Gland ◽

Plasma Levels ◽

Seasonal Changes ◽

Peak Plasma ◽

Plasma Concentrations

Two experiments were carried out to study the effects of controlled lighting régimes on plasma levels of LH, testosterone and prolactin in Romney rams. In the second experiment the rams were either pinealectomized or sham-operated so that the role of the pineal gland in mediating seasonal changes in reproduction could be examined. Levels of testosterone and prolactin were considerably influenced by the lighting schedule. Peak plasma concentrations of testosterone were associated with periods during which the daily photoperiod decreased, whereas plasma levels of prolactin showed a pattern of changes approximately in phase with the lighting cycles. Mean plasma concentrations of LH were low in all groups of rams, which made the detection of significant effects of any treatment very unlikely. Pinealectomy reduced the effects of changes in the daily photoperiod on the patterns of secretion of testosterone and prolactin. These findings establish the pineal gland as an organ which influences the endocrine responses of rams to photoperiodic stimuli and it is concluded that the pineal gland is probably important as a mediator of seasonal reproductive changes in these animals.

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Arterial and Venous Pharmacokinetics of Ropivacaine with and without Epinephrine after Thoracic Paravertebral Block

Anesthesiology ◽

10.1097/00000542-200510000-00008 ◽

2005 ◽

Vol 103 (4) ◽

pp. 704-711 ◽

Cited By ~ 55

Author(s):

Manoj K. Karmakar ◽

Anthony M.-H. Ho ◽

Bonita K. Law ◽

April S. Y. Wong ◽

Steven L. Shafer ◽

...

Keyword(s):

Peak Plasma ◽

Venous Blood ◽

Plasma Concentrations ◽

Paravertebral Block ◽

Inverse Gaussian ◽

Absorption Function ◽

Thoracic Paravertebral Block ◽

Gaussian Density ◽

Absorption Phase ◽

Slow Absorption

Background Animal and volunteer studies indicate that ropivacaine is associated with less neurologic and cardiac toxicity than bupivacaine. Ropivacaine may offer advantages when used for thoracic paravertebral block. This study was designed to describe the pharmacokinetics of ropivacaine after thoracic paravertebral block. Methods Twenty female patients undergoing elective unilateral breast surgery were randomly assigned to receive a single bolus thoracic paravertebral injection of 2 mg/kg ropivacaine, with or without 5 mug/ml epinephrine. Simultaneous arterial and venous blood samples were obtained for plasma ropivacaine assay. Data were analyzed with NONMEM, using two possible absorption models: conventional first-order absorption and absorption following the inverse gaussian density function. Results Epinephrine reduced the peak plasma concentrations and delayed the time of peak concentration of ropivacaine in both the arterial and venous blood. The time course of drug input into the systemic circulation was best described by two inverse gaussian density functions. The median bioavailability of the rapid component was approximately 20% higher when epinephrine was not used. The mean absorption times were 7.8 min for the rapid absorption phase and 697 min for the slow absorption phase, with wide dispersion of the absorption function for the acute phase. The half-time of arterial-venous equilibration was 1.5 min. Conclusion The absorption of ropivacaine after thoracic paravertebral block is described by rapid and slow absorption phases. The rapid phase approximates the speed of intravenous administration and accounts for nearly half of ropivacaine absorption. The addition of 5 mug/ml epinephrine to ropivacaine significantly delays its systemic absorption and reduces the peak plasma concentration.

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Plasma Adipokines in Patients Resuscitated from Cardiac Arrest: Difference of Visfatin between Survivors and Nonsurvivors

Disease Markers ◽

10.1155/2020/9608276 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Yuan-Zhuo Chen ◽

Shu-Qin Zhou ◽

Yan-Qing Chen ◽

Hu Peng ◽

Yu-Gang Zhuang

Keyword(s):

Cardiac Arrest ◽

Plasma Levels ◽

Fatty Acid Binding Protein ◽

Operating Characteristic ◽

Characteristic Curve ◽

Venous Blood ◽

Plasma Concentrations ◽

Spontaneous Circulation ◽

Apache Ii Score ◽

Fatty Acid Binding

Background. Adipokines are a group of cytokines or peptides secreted by adipose tissue to exert numerous biological functions. In the present study, we measured the plasma levels of four adipokines (adiponectin, leptin, fatty acid-binding protein 4 (FABP4), and visfatin) in cardiac arrest patients following return of spontaneous circulation (ROSC). Methods. Totally, 21 patients who experienced cardiac arrest and successful ROSC with expected survival of at least 48 hours (from January 2016 to December 2017) were consecutively enrolled into this prospective observational clinical study. Of the 21 enrolled patients, ten survived, and other eleven died between 2 days and 6 months post ROSC. Venous blood was drawn at three time points: baseline (<1 hour post ROSC), 2 days post ROSC, and 7 days post ROSC. Plasma concentrations of adiponectin, leptin, FABP4, and visfatin were determined using commercial enzyme-linked immunosorbent assays. Results. The plasma visfatin levels at 2 or 7 days post ROSC increased significantly compared with the baseline (P<0.01), while plasma levels of adiponectin, leptin, and FABP4 did not change. Moreover, plasma visfatin levels in survivors at 2 or 7 days post ROSC were higher than those in nonsurvivors (P<0.01). Plasma visfatin levels at 2 or 7 days post ROSC were negatively correlated with Acute Physiology and Chronic Health Evaluation (APACHE) II score and time to ROSC. Moreover, receiver operating characteristic curve analysis showed that the plasma visfatin levels at 2 or 7 days post ROSC were good predictors for survival of the patients. Conclusion. Elevated plasma visfatin levels may be a marker for better outcome of cardiac arrest patients post ROSC.

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Intranasal Cocaine: Dose Relationships of Psychological Effects and Plasma Levels

The International Journal of Psychiatry in Medicine ◽

10.2190/5x0n-twkj-ggy6-t10n ◽

1983 ◽

Vol 12 (1) ◽

pp. 1-13 ◽

Cited By ~ 31

Author(s):

Craig Van Dyke ◽

James Ungerer ◽

Peter Jatlow ◽

Paul Barash ◽

Robert Byck

Keyword(s):

Plasma Concentration ◽

Plasma Levels ◽

Peak Plasma ◽

Plasma Concentrations ◽

Psychological Effects ◽

Acute Tolerance ◽

Lidocaine Hydrochloride ◽

Intranasal Cocaine ◽

Cocaine Hydrochloride ◽

Repeated Doses

We compared the psychological effects of three doses of intranasal cocaine hydrochloride (.2, .75, and 1.5 mg/kg) with cocaine plasma concentrations in four volunteers. Intranasal lidocaine hydrochloride (.2 mg/kg) was used as a topically active placebo. Peak “high” ratings were related to both dose and peak plasma concentrations. At a given plasma concentration, “high” ratings were greater when plasma levels were increasing than when they were decreasing. This indicates that acute tolerance by tachyphylaxis occurred after single doses. The cocaine “high” was a pleasant feeling but was without distinctive sensations. The dramatic effects of intranasal cocaine on the street may be related to larger or repeated doses as well as the setting.

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Important pharmacogenomic aspects in the management of HIV/AIDS

South African Family Practice ◽

10.4102/safp.v61i1.5047 ◽

2019 ◽

Vol 61 (1) ◽

Author(s):

A. Marais ◽

E. Osuch ◽

V. Steenkamp ◽

L. Ledwaba

Keyword(s):

South African ◽

Plasma Levels ◽

Drug Exposure ◽

Peak Plasma ◽

Plasma Concentrations ◽

Metabolizing Enzymes ◽

Highly Active ◽

Adequate Dosage ◽

Hiv Aids

In managing HIV/AIDS with highly active antiretroviral agents, the historical therapeutic aim remains to maintain the plasma concentrations at a level above the half maximal inhibitory concentration (IC50) required for 50% inhibition in viral replication. Concentration dependent toxicity is often observed in patients with elevated drug exposure and high peak plasma levels in lieu of accurately calculated drug dosages. Similarly low plasma concentrations are frequently witnessed in individuals receiving adequate dosage regimens. Pharmacogenetic variations in drug metabolizing enzymes may contribute to this phenomenon. Over the last decade, knowledge about the role of pharmacogenetics in the treatment and prediction of ARV plasma levels have increased significantly. However, the extent of these genetic variations remain largely unknown in the South African population, which has sparked a renewed enthusiasm for local pharmacogenetic studies.

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A Comparison of the Absorption of Two Formulations of Paracetamol

Journal of International Medical Research ◽

10.1177/030006057300100606 ◽

1973 ◽

Vol 1 (6) ◽

pp. 548-550 ◽

Cited By ~ 7

Author(s):

A Hedges ◽

C M Kaye

Keyword(s):

Plasma Levels ◽

Peak Plasma ◽

Plasma Concentrations ◽

Tablet Formulation ◽

Chromatographic Technique ◽

Rapid Absorption ◽

Human Volunteers ◽

Normal Human ◽

Liquid Chromatographic

The absorption of two formulations of paracetamol was compared in four normal human volunteers. A cross-over study was employed in which each was given the tablet or effervescent formulation with a seven day interval between medications. Plasma levels of paracetamol were measured up to four hours after administration using a gas-liquid chromatographic technique. The tablet formulation (Panadol) gave rise to peak plasma levels at times varying from less than thirty minutes to two hours, while the effervescent formulation (Para-seltzer) gave rise to higher plasma concentrations of paracetamol in three of the four volunteers and peak levels occurred at or before thirty minutes in all four volunteers, indicating a more rapid absorption of the effervescent formulation.

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EFFECT OF VENOUS STASIS ON THE RELEASE OF VON WILLEERAND FACTOR ANTIGEN (VWF:AG) AND PLASMINOGEN ACTIVATOR (PA) IN PATIENTS WITH THROMBOEMBOLISM

10.1055/s-0038-1644432 ◽

1987 ◽

Author(s):

T Uchiyama ◽

M Matsumoto ◽

N Narahara ◽

H Tanaka ◽

N Kobayashi ◽

...

Keyword(s):

Plasma Level ◽

Significant Relationship ◽

Plasma Levels ◽

Venous Blood ◽

Venous Occlusion ◽

Venous Stasis ◽

Common Mechanism ◽

Control Group ◽

Endothelial Cell Function ◽

Before And After

Plasma levels of vWF:Ag and PA (both activity and antigen) present in the venous blood were studied in 114 patients with arterial thromboembolic disease and 30 age matched healthy individuals. In 29 cases of the patient group (patients) and 7 cases of the control group (controls), turnover of intravenously injected 1-125-fibrinogen was studied. Venous blood was obtained from the antecubital vein of subjects before and after 5 minutes0' of venous occlusion. vWF:Ag was determined by electroimmunodiffusion (Laurell0's method). PA activity was measured by the method of Campbell et al, and PA antigen was assayed by ELISA kit purchased from BioPool Co. And the following results were obtained : 1) Mean plasma level of vWF:Ag was significantly higher (p<0.001) and mean plasma level of PA activity was significantly lower (p<0.05) in patients than in controls both before and after the venous occlusion. 2) Mean plasma level of PA antigen was significantly higher (p<0.01) in patients (mean+SD; 4.05j±1.58 ng/ml) than in controls (2.95±1.11 ng/ml) before the venous occlusion. The mean specific acitivity of PA was significantly lower (p<0.01) in patients than in controls both before and after the venous occlusion. 3) Plasma half life (T/2) of fibrinogen was significantly shorter (p<0.001) and catabolic flux (J3X) of fibrinogen was significantly higher (p<0.001) in patients tahn in controls. 4) Significant relationship was observed between T/2 of fibrinogen and plasma levels of vWF:Ag before and after the venous occlusion, PA activities after the occlusion, and levels of PA antigen before the occlusion. 5) Significant relationship was also observed between J3X of fibrinogen and plasma levels of vWF:Ag before and after the verous occlusion, PA activities after the occlusion, and levels of PA antigen before the occlusion. These results suggests that the changes in endothelial cell function might be a common mechanism responsible for the abnormal findings in plasma levels of both vWF:Ag and PA and for the acceleration of fibrinogen metabolism.

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Plasma Levels of Matrix Metalloprotease MMP-9 and Tissue Inhibitor TIMP-1 in Caucasian Patients with Polypoidal Choroidal Vasculopathy

Vision ◽

10.3390/vision4020027 ◽

2020 ◽

Vol 4 (2) ◽

pp. 27

Author(s):

Jakob Ø. Sørensen ◽

Yousif Subhi ◽

Christopher R. Molbech ◽

Marie Krogh Nielsen ◽

Torben L. Sørensen

Keyword(s):

Extracellular Matrix ◽

Plasma Levels ◽

Polypoidal Choroidal Vasculopathy ◽

Venous Blood ◽

Plasma Concentrations ◽

Healthy Controls ◽

Tissue Inhibitor ◽

Asian Patients ◽

Caucasian Patients ◽

Choroidal Vasculopathy

Background: Matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) are regulating enzymes of the extracellular matrix. A systemic imbalance of MMP-9 and TIMP-1, thought to reflect an imbalance of the extracellular matrix homeostasis, is previously associated with polypoidal choroidal vasculopathy (PCV) in Asian patients. Previous studies suggest inter-ethnical differences in the genetic background and etiology of PCV. To further explore this issue, we studied the plasma levels of MMP-9 and TIMP-1 in Caucasian patients with PCV and compared to healthy age-matched controls. Methods: For this prospective case-control study, 60 participants were recruited who were either patients with PCV (n = 26) or healthy controls (n = 34). All participants underwent detailed clinical examination. We sampled fresh venous blood, isolated plasma, and quantified plasma concentrations of the extracellular matrix regulators MMP-9 and TIMP-1 using electrochemiluminescence immunoassays. Results: Plasma levels of MMP-9 (p = 0.4), TIMP-1 (p = 0.9), and MMP-9/TIMP-1 ratio (p = 0.4) did not differ significantly between patients with PCV and healthy controls. No differences appeared after adjusting for influencing co-variates in multivariate analyses. Conclusion: We demonstrate that Caucasian patients with PCV do not have altered levels of plasma MMP-9 or plasma TIMP-1. These findings suggest no strong evidence of a systemic imbalance of the extracellular matrix homeostasis in Caucasian patients with PCV. Our findings are in line with studies of other aspects of PCV that are also subject to significant inter-ethnical differences.

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GRN163L, a Potent and Specific Inhibitor of Telomerase: Integrated Pharmacokinetic, Pharmacodynamic, and Safety Data Guides Design of Practical Treatment Regimens for Targeting Inhibitory Levels in Patients.

Blood ◽

10.1182/blood.v108.11.2595.2595 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2595-2595 ◽

Cited By ~ 1

Author(s):

Robert J. Tressler ◽

Allison C. Chin ◽

Eric J. Feldman ◽

Kanti R. Rai ◽

Doug Kornbrust ◽

...

Keyword(s):

Clinical Trials ◽

Complement Activation ◽

Plasma Levels ◽

Peak Plasma ◽

Plasma Concentrations ◽

Safety Data ◽

Specific Inhibitor ◽

Human Tumor ◽

Human Tumor Xenograft ◽

Telomerase Inhibition

Abstract GRN163L is a lipidated thiophosphoramidate oligonucleotide that binds with nanomolar affinity to the template region of human telomerase RNA, causing direct enzyme inhibition. Cellular IC50 values range from 0.8 to 6.5 μg/mL among 13 solid and hematologic tumor lines, and GRN163L inhibits tumor growth in multiple human tumor xenograft studies. Due to the high affinity and slow off-rate of binding, telomerase inhibition is long-lasting following exposure to the drug (Oncogene, 2005, 24, 5262). Previously reported studies demonstrated that exposure of human myeloma cell lines INA6 and ARP to 1 μM GRN163L resulted in ≥ 90% inhibition of telomerase activity and was followed by reduced cell growth and survival (Masood et al, ASH 2005). GRN163L uptake and telomerase inhibition have also been demonstrated in primary human CLL cells tested at 2 μM (Lin et al., ASH, 2005). Many polyanionic oligonucleotides can cause reversible inhibition of the intrinsic coagulation pathway and complement activation at high concentrations. The studies reported here were designed to determine safe and well-tolerated dose schedules and dose ranges for GRN163L in primates in order to attain plasma levels effective for telomerase inhibition and anti-tumor effects. Methods: GRN163L was administered i.v. to cynomolgus monkeys at varying doses and infusion durations. Plasma levels were determined using a validated hybridization-ELISA method. Results: In multiple studies, the T½α from two compartment modeling was 2.9 to 5.3 hr for doses of 5 to 15 mg/kg. Actual (from separate but representative studies) and modeled peak plasma levels (Cmax) as well as duration of plasma levels above the 1 μM (~4.8 μg/mL) cellular telomerase inhibitory level are shown in the table below. 5 mg/kg dose Observed Cmax From Model Inf Dur Mean ±SD Cmax Level ≥ 1 μg/ml hrs μg/ml hrs Bolus 185±8 153 15 0.5 200±16 144 16 2 128±3 122 16 6 63±9 83 19 At 10 mg/kg over 6 h, Cmax was 90–115 μg/mL, with < 2-fold increases in APTT and no significant complement activation. Repeated doses up to 15 mg/kg were well tolerated at all infusion durations. A Phase I/II clinical trial of GRN163L infusions in CLL patients is in progress and the observed T½α values from initial cohorts are consistent with the model presented here. Conclusions: Due to the relatively long T½α of GRN163L, telomerase inhibitory concentrations should be attainable with clinically practical infusions of 1 to 6 hr duration without dose-limiting peak plasma concentrations. Given the high target affinity, such infusions repeated intermittently could maintain near continual target inhibition. GRN163L is the first telomerase targeted agent to enter clinical trials. Initial results from these clinical trials support the hypothesis that telomerase inhibitory levels can be achieved at well tolerated doses.

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