A study to evaluate the first dose of gentamicin needed to achieve a peak plasma concentration of 30 mg/l in patients hospitalized for severe sepsis

2016 ◽  
Vol 35 (7) ◽  
pp. 1187-1193 ◽  
Author(s):  
N. Allou ◽  
Y. Charifou ◽  
P. Augustin ◽  
T. Galas ◽  
D. Valance ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Plasma Concentration ◽  
Peak Plasma ◽  
Peak Plasma Concentration

Pharmacokinetics of Rapacuronium in Infants and Children with Intravenous and Intramuscular Administration

2000 ◽  
Vol 92 (2) ◽  
pp. 376-376 ◽  
Author(s):  
Lynne M. Reynolds ◽  
Andrew Infosino ◽  
Ronald Brown ◽  
Jim Hsu ◽  
Dennis M. Fisher
Keyword(s):  
Plasma Concentration ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Pediatric Anesthesia ◽  
Infants And Children ◽  
Intramuscular Administration ◽  
Pharmacokinetic Analysis ◽  
Intravenous Route ◽  
Population Pharmacokinetic ◽  
In Infants And Children

Background A nondepolarizing muscle relaxant with an onset and offset profile similar to succinylcholine is desirable for pediatric anesthesia. The onset and offset of rapacuronium are rapid in children. In the current study, the authors determined its pharmacokinetic characteristics in children. In addition to administering rapacuronium by the usual intravenous route, the authors also gave rapacuronium intramuscularly to determine uptake characteristics and bioavailability. Methods Forty unpremedicated patients aged 2 months to 3 yr were anesthetized with halothane, 0.82-1.0% end-tidal concentration. When anesthetic conditions were stable, rapacuronium was injected either into a peripheral vein (2 mg/kg for infants, 3 mg/kg for children) or a deltoid muscle (2.8 mg/kg for infants, 4.8 mg/kg for children). Four venous plasma samples were obtained from each subject 2-240 min after rapacuronium administration. A mixed-effects population pharmacokinetic analysis was applied to these values to determine bioavailability, absorption rate constant, and time to peak plasma concentration with intramuscular administration. Results Plasma clearance was 4.77 ml x kg(-1) x min(-1) + 8.48 ml/min. Intramuscular bioavailability averaged 56%. Absorption from the intramuscular depot had two rate constants: 0.0491 min(-1) (72.4% of absorbed drug) and 0.0110 min(-1) (27.6% of the absorbed drug). Simulation indicated that plasma concentration peaks 4.0 and 5.0 min after intramuscular rapacuronium in infants and children, respectively, and that, at 30 min, less than 25% of the administered dose remains to be absorbed from the intramuscular depot. Conclusions In infants and children, rapacuronium's clearance and steady state distribution volume are less than in adults. After intramuscular administration, bioavailability is 56%, and plasma rapacuronium concentrations peak within 4 or 5 min.

scholarly journals Effect of food on the pharmacokinetics and therapeutic efficacy of 4-phenylbutyrate in progressive familial intrahepatic cholestasis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Satoshi Nakano ◽  
Shuhei Osaka ◽  
Yusuke Sabu ◽  
Kei Minowa ◽  
Saeko Hirai ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Intrahepatic Cholestasis ◽  
Clinical Symptoms ◽  
Peak Plasma ◽  
Oral Treatment ◽  
Peak Plasma Concentration ◽  
Open Label ◽  
Time Curve ◽  
Single Dose Study ◽  
Progressive Familial Intrahepatic Cholestasis

AbstractProgressive familial intrahepatic cholestasis (PFIC), a rare inherited disorder, progresses to liver failure in childhood. We have shown that sodium 4-phenylbutyrate (NaPB), a drug approved for urea cycle disorders (UCDs), has beneficial effects in PFIC. However, there is little evidence to determine an optimal regimen for NaPB therapy. Herein, a multicenter, open-label, single-dose study was performed to investigate the influence of meal timing on the pharmacokinetics of NaPB. NaPB (150 mg/kg) was administered orally 30 min before, just before, and just after breakfast following overnight fasting. Seven pediatric PFIC patients were enrolled and six completed the study. Compared with postprandial administration, an approved regimen for UCDs, preprandial administration significantly increased the peak plasma concentration and area under the plasma concentration-time curve of 4-phenylbutyrate by 2.5-fold (95% confidential interval (CI), 2.0–3.0;P = 0.003) and 2.4-fold (95% CI, 1.7–3.2;P = 0.005). The observational study over 3 years in two PFIC patients showed that preprandial, but not prandial or postprandial, oral treatment with 500 mg/kg/day NaPB improved liver function tests and clinical symptoms and suppressed the fibrosis progression. No adverse events were observed. Preprandial oral administration of NaPB was needed to maximize its potency in PFIC patients.

Safety, Tolerability, and Pharmacokinetics of Sumatriptan in Healthy Subjects Following Ascending Single Intranasal Doses and Multiple Intranasal Doses

Cephalalgia ◽  
1997 ◽  
Vol 17 (4) ◽  
pp. 541-550 ◽  
Author(s):  
KHP Moore ◽  
EK Hussey ◽  
S Shaw ◽  
E Fuseau ◽  
C Duquesnoy ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Adverse Events ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Dose Range ◽  
Maximum Plasma ◽  
Multiple Doses ◽  
To Receive ◽  
Intranasal Spray ◽  
Female Subjects

The delivery of sumatriptan doses intranasally could add greater flexibility in the treatment of migraine than is possible with the currently available subcutaneous and oral sumatriptan preparations. Two independent double-blind, randomized, placebo-controlled clinical studies were conducted to evaluate the safety, tolerability and pharmacokinetics of intranasally administered sumatriptan following ascending single doses (three different dose levels) and multiple doses. In the four-way crossover, ascending-dose study, 20 healthy female subjects were randomized to receive on separate occasions single intranasal spray doses of 5, 10, or 20 mg sumatriptan (as the hemisulphate salt) or placebo into one nostril. Adverse events were mild and consisted mainly of bitter taste at the back of the throat and events typical of sumatriptan administered by other routes (headache, lightheadedness and tingling). Area under the plasma sumatriptan concentration versus time curve (AUC) and peak plasma concentration (Cmax) increased with the dose. Dose proportionality was demonstrated between 5 and 10 mg but not across the dose range 5–20 mg. Time to maximum plasma concentration (tmax) was variable due to multiple peaking. The elimination half-life (t1/2), approximately 2 h, was unaffected by the magnitude of dose. In the two-period, multiple-dose, crossover study, 12 healthy adult male and female subjects were randomized to receive either sumatriptan hemisulphate 20 mg or placebo, administered intranasally as a spray three times a day for 4 days, The two dosing periods were separated by 3 to 14 days. Multiple doses of sumatriptan were well tolerated, with no serious adverse events occurring or withdrawals due to adverse events. All patients reported a mild to moderate drug-related disturbance of taste. Nasal examinations remained normal, and olfactory function was unaffected. The AUC over the first 8 h following dosing (AUC8) and fraction of the dose excreted in the urine (fe; 6.2% vs 3.6%) were similar on Days 1 and 4. Day 4 values were significantly higher (p0.05) for Cmax (16.9 ng/ml vs 13.1 ng/ml), renal clearance (Clr; 19.0 l/h vs 14.2 l/h), and t1/2 (2.18 h vs 1.93 h), and shorter for tmax (0.88 h vs 1.75 h). Some accumulation (22%) occurred over the 4 days of dosing. Serum concentrations of the pharmacologically inactive indole acetic acid metabolite of sumatriptan were fourfold to fivefold higher than corresponding sumatriptan concentrations. Overall, these studies show the sumatriptan intranasal spray formulation is well tolerated, allows rapid absorption of sumatriptan, and results in only a clinically insignificant degree of sumatriptan accumulation upon repeated dosing.

scholarly journals BIOAVAILABILITY AND DISPOSITION KINETICS OF AMOXICILLIN

2015 ◽  
Vol 22 (01) ◽  
pp. 006-012
Author(s):  
Zulfiqar-Ul- Hassan ◽  
Sualeha Riffat ◽  
Aamir Nazir ◽  
Rahat Naseer ◽  
Anila Asghar ◽  
...  
Keyword(s):  
Body Weight ◽  
Plasma Concentration ◽  
Cell Volume ◽  
Packed Cell Volume ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Assay Method ◽  
Intravenous Route ◽  
Disposition Kinetics ◽  
Kinetics Of

OBJECTIVE: The study was planned to observe the bioavailability anddisposition kinetics of amoxicillin in adult rabbits (irrespective of sex) under healthy anddehydrated conditions. Design: Comparative. Place and duration of study: The study wasconducted at the department of pharmacology, University of Veterinary and Animal Sciences,Lahore from April 2013 to October 2013. Methodology: Initially all rabbits were weighed andtheir packed cell volume (PCV) and other biochemical parameters were observed under normalconditions. Bioavailability and disposition kinetics of amoxicillin (10mg/kg body weight) werestudied in normal rabbits following oral and intravenous route of drug administration. After 10days washout period, these rabbits were made dehydrated by keeping the animals off waterbut not food. The animals with 10% decrease in body weight were declared dehydrated. Theirparameters were again measured. Treated rabbits were administered amoxicillin orally andintravenously (10mg/kg body weight). Samples were drawn at prescribed time. Amoxicillinwas assessed in plasma by using microbiological assay method. Plasma concentration wasanalyzed using non compartmental method. Results: The water deprived or dehydrated rabbitsshowed a significant increase in the packed cell volume, blood glucose and plasma globulins ascompared to the normal rabbits. However, there was a significant (p<0.05 & p<0.01) decreasein body weight, total proteins, albumins and albumin globulin ratio of the dehydrated rabbits.The peak plasma concentration, volume of distribution and rate constant of elimination waslower in the dehydrated rabbits as compared to the normal rabbits. The plasma concentrationof amoxicillin after intravenous administration in dehydrated rabbits had a significant (p<0.05& p<0.01) larger area under curve, area under 1st moment curve, a longer half life and a largermean residence time. Conclusions: The study in the dehydrated rabbits indicated the need ofmodification of dosage regimen.

scholarly journals The Effect of Pre-Postnatal Nicotine Exposure on Types and Levels of Plasma Sialic Acids in Rats

Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1546
Author(s):  
Soycan Mizrak ◽  
Umut Sahar ◽  
Afrooz Rashnonejad ◽  
Remziye Deveci ◽  
Gulinnaz Ercan
Keyword(s):  
Sialic Acid ◽  
Plasma Concentration ◽  
Half Life ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Albino Rats ◽  
Nicotine Administration ◽  
Wide Range ◽  
Concentration Changes ◽  
Per Oral

Nicotine, is an alkaloid compound consisting of pyridine and pyrolidine ring. Its closed formula is C10H4N2. During smoking peak plasma concentration changes from 25 to 50 ng/mL. Its half-life is 1–2 h. Nicotine is metabolized primarily in the liver and excreted by the kidneys. The plasma concentration of the nicotine metabolite cotinine is 10 times more than nicotine and its half-life is longer around 15 to 20 h. Cotinine can be found in both amniotic fluid and umbilical cord blood given that it passes across the placental barrier. Adverse effects of nicotine and its metabolites on the fetus are suggested but have not been proven by scientific explanations till now. Sialic acid (Sia) is a modified nine-carbon sugar. They are located on the last end of the glycan chains located in the glycoconjugate structures. They organize a wide range of relationships between cells and their environment such as cellular recognition, adhesion, transmission, differentiation and aging. The aim of this study is to determine the possible changes in the sialic acid levels and types in the plasma after different levels of nicotine applied to Swiss Albino rats in order to assess the effect of long-term per oral nicotine administration.

scholarly journals Assessment of Metabolic Interaction between Repaglinide and Quercetin via Mixed Inhibition in the Liver: In Vitro and In Vivo

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 782
Author(s):  
Ji-Min Kim ◽  
Seong-Wook Seo ◽  
Dong-Gyun Han ◽  
Hwayoung Yun ◽  
In-Soo Yoon
Keyword(s):  
Plasma Concentration ◽  
Liver Microsome ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Systemic Exposure ◽  
Concurrent Administration ◽  
Time Curve ◽  
Mixed Inhibition

Repaglinide (RPG), a rapid-acting meglitinide analog, is an oral hypoglycemic agent for patients with type 2 diabetes mellitus. Quercetin (QCT) is a well-known antioxidant and antidiabetic flavonoid that has been used as an important ingredient in many functional foods and complementary medicines. This study aimed to comprehensively investigate the effects of QCT on the metabolism of RPG and its underlying mechanisms. The mean (range) IC50 of QCT on the microsomal metabolism of RPG was estimated to be 16.7 (13.0–18.6) μM in the rat liver microsome (RLM) and 3.0 (1.53–5.44) μM in the human liver microsome (HLM). The type of inhibition exhibited by QCT on RPG metabolism was determined to be a mixed inhibition with a Ki of 72.0 μM in RLM and 24.2 μM in HLM as obtained through relevant graphical and enzyme inhibition model-based analyses. Furthermore, the area under the plasma concentration versus time curve (AUC) and peak plasma concentration (Cmax) of RPG administered intravenously and orally in rats were significantly increased by 1.83- and 1.88-fold, respectively, after concurrent administration with QCT. As the protein binding and blood distribution of RPG were observed to be unaltered by QCT, it is plausible that the hepatic first-pass and systemic metabolism of RPG could have been inhibited by QCT, resulting in the increased systemic exposure (AUC and Cmax) of RPG. These results suggest that there is a possibility that clinically significant pharmacokinetic interactions between QCT and RPG could occur, depending on the extent and duration of QCT intake from foods and dietary supplements.

scholarly journals Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Vaborbactam and Meropenem Alone and in Combination following Single and Multiple Doses in Healthy Adult Subjects

2018 ◽  
Vol 62 (4) ◽  
Author(s):  
Christopher M. Rubino ◽  
Sujata M. Bhavnani ◽  
Jeffery S. Loutit ◽  
Elizabeth E. Morgan ◽  
Dan White ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Healthy Adult ◽  
Clinical Investigation ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Double Blind Study ◽  
Time Curve ◽  
Time Zero ◽  
Concentration Time ◽  
Plasma Concentration Time Curve

ABSTRACTMeropenem-vaborbactam is a fixed combination of the novel β-lactamase inhibitor vaborbactam and the carbapenem antibiotic meropenem, developed for the treatment of serious infections caused by drug-resistant Gram-negative bacteria. The safety, tolerability, and pharmacokinetics (PK) of vaborbactam and meropenem following single and multiple ascending doses of each study drug administered alone or combined were evaluated in 76 healthy adult subjects in a randomized, placebo-controlled, double-blind study. Subjects were enrolled in 1 of 5 dose cohorts (receiving 250 to 2,000 mg vaborbactam and/or 1,000 to 2,000 mg meropenem) alone or in combination. No subjects discontinued the study due to adverse events (AEs), and no serious AEs were observed. The pharmacokinetics of meropenem and vaborbactam were similar when given alone or in combination; all evaluated plasma PK exposure measures (peak plasma concentration, area under the plasma concentration-time curve [AUC] from time zero to the last measurable concentration area under the plasma concentration-time curve, and AUC from time zero to infinity) were similar for the study drugs alone versus those in combination, indicating no pharmacokinetic interaction between meropenem and vaborbactam. Across all treatments, 47 to 64% of an administered meropenem dose and 75 to 95% of vaborbactam was excreted unchanged in the urine over 48 h postdose. Meropenem and vaborbactam, when given alone or in combination, have similar pharmacokinetic properties, with no plasma or urine PK drug-drug interactions, and are well tolerated. These findings supported further clinical investigation of the combination product. (This study is registered at ClinicalTrials.gov under registration no. NCT01897779.)

scholarly journals Plasma appearance and disappearance of an oral dose of 25-hydroxyvitamin D2in healthy adults

2011 ◽  
Vol 107 (8) ◽  
pp. 1128-1137 ◽  
Author(s):  
Kerry S. Jones ◽  
Inez Schoenmakers ◽  
Les J. C. Bluck ◽  
Shujing Ding ◽  
Ann Prentice
Keyword(s):  
Vitamin D ◽  
Plasma Concentration ◽  
Oral Dose ◽  
Half Life ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Post Dose ◽  
Vitamin D Metabolism ◽  
Blood Samples ◽  
Potential Biomarker

25-Hydroxyvitamin D (25(OH)D) half-life is a potential biomarker for investigating vitamin D metabolism and requirements. We performed a pilot study to assess the approach and practical feasibility of measuring 25(OH)D half-life after an oral dose. A total of twelve healthy Gambian men aged 18–23 years were divided into two groups to investigate the rate and timing of (1) absorption and (2) plasma disappearance after an 80 nmol oral dose of 25(OH)D2. Fasting blood samples were collected at baseline and, in the first group, every 2 h post-dose for 12 h, at 24 h, 48 h and on day 15. In the second group, fasting blood samples were collected on days 3, 4, 5, 6, 9, 12, 15, 18 and 21. Urine was collected for 2 h after the first morning void at baseline and on day 15. 25(OH)D2plasma concentration was measured by ultra-performance liquid chromatography-tandem MS/MS and corrected for baseline. Biomarkers of vitamin D, Ca and P metabolism were measured at baseline and on day 15. The peak plasma concentration of 25(OH)D2was 9·6 (sd0·9) nmol/l at 4·4 (sd1·8) h. The terminal slope of 25(OH)D2disappearance was identified to commence from day 6. The terminal half-life of plasma 25(OH)D2was 13·4 (sd2·7) d. There were no significant differences in plasma 25(OH)D3, total 1,25(OH)2D, parathyroid hormone, P, Ca and ionised Ca and urinary Ca and P between baseline and day 15 and between the two groups. The present study provides data on the plasma response to oral 25(OH)D2that will underpin and contribute to the further development of studies to investigate 25(OH)D half-life.

scholarly journals Vitamin K absorption and kinetics in human subjects after consumption of13C-labelled phylloquinone from kale

2010 ◽  
Vol 104 (6) ◽  
pp. 858-862 ◽  
Author(s):  
Janet A. Novotny ◽  
Anne C. Kurilich ◽  
Steven J. Britz ◽  
David J. Baer ◽  
Beverly A. Clevidence
Keyword(s):  
Plasma Concentration ◽  
Detection Limit ◽  
Vitamin K ◽  
Peak Plasma ◽  
Human Subjects ◽  
Peak Plasma Concentration ◽  
Plasma Samples ◽  
Time Data ◽  
Compartmental Modelling ◽  
Concentration Time

The absorption and plasma disappearance of vitamin K were investigated by uniformly labelling phylloquinone in kale with carbon-13, and by feeding the kale to study subjects. Seven healthy volunteers ingested a single 400 g serving of kale with 30 g vegetable oil. The kale provided 156 nmol of phylloquinone. Serial plasma samples were collected and analysed for the appearance of13C-phylloquinone by HPLC–MS. Six of the subjects showed significant amounts of labelled phylloquinone in plasma, though one subject's plasma was not consistently enriched above the detection limit, and this subject's baseline plasma phylloquinone level was the lowest in the group. After ingestion of the labelled kale, plasma13C-phylloquinone concentration increased rapidly to a peak between 6 and 10 h, and then rapidly decreased. Average peak plasma concentration for the six subjects with detectable13C-phylloquinone was 2·1 nmol/l. Plasma concentration–time data were analysed by compartmental modelling. Modelling results demonstrated a mean (n6) bioavailability of phylloquinone from kale to be 4·7 %. Plasma and tissue half-times for phylloquinone were found to be 8·8 and 215 h, respectively.

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