scholarly journals Pharmacokinetic modeling of morphine and its glucuronides: Comparison of nebulization versus intravenous route in healthy volunteers

2021 ◽  
Author(s):  
Thomas Duflot ◽  
Tony Pereira ◽  
Marie‐Pierre Tavolacci ◽  
Robinson Joannidès ◽  
Frédéric Aubrun ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Pharmacokinetic Modeling ◽  
Intravenous Route

scholarly journals Single-dose pharmacokinetics of temocillin in plasma and soft tissues of healthy volunteers after intravenous and subcutaneous administration: a randomized crossover microdialysis trial

2020 ◽  
Vol 75 (9) ◽  
pp. 2650-2656 ◽  
Author(s):  
Peter Matzneller ◽  
Perrin Ngougni Pokem ◽  
Arnaud Capron ◽  
Edith Lackner ◽  
Beatrix Wulkersdorfer ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Protein Binding ◽  
Healthy Volunteers ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Soft Tissues ◽  
Therapeutic Option ◽  
Subcutaneous Administration ◽  
Intravenous Route ◽  
Drug Concentrations

Abstract Background The antibiotic temocillin has recently been rediscovered as a promising therapeutic option against MDR Gram-negative bacteria. However, some aspects of the pharmacokinetic (PK) profile of the drug are still to be elucidated: subcutaneous administration of temocillin might be of interest as an alternative to the intravenous route in selected patients. Similarly, information on the penetration of temocillin into human soft tissues is lacking. Objectives To investigate the feasibility and plasma PK of subcutaneous dosing as well as soft tissue PK of temocillin after intravenous administration to healthy volunteers. Methods Eight healthy volunteers received 2 g of temocillin both as intravenous and subcutaneous infusion in a randomized two-period crossover study. Concentration–time profiles of total temocillin in plasma (after both routes) and of unbound temocillin in plasma, muscle and subcutis (only after intravenous dosing) were determined up to 12 h post-dose. Results Subcutaneous dosing caused some infusion site discomfort but resulted in sustained drug concentrations over time with only slightly decreased overall exposure compared with intravenous dosing. Plasma protein binding of temocillin showed concentration-dependent behaviour and was higher than previously reported. Still, unbound drug concentrations in muscle and subcutis determined by microdialysis markedly exceeded those in plasma, suggesting good tissue penetration of temocillin. Conclusions The subcutaneous administration of temocillin is a valid and feasible alternative to intravenous dosing. With the description of plasma protein binding and soft tissue PK of temocillin in healthy volunteers, this study provides important information that adds to the ongoing characterization of the PK profile of temocillin and might serve as input for PK/PD considerations.

scholarly journals Pharmacokinetic Modeling of Plasma and Intracellular Concentrations of Raltegravir in Healthy Volunteers

2011 ◽  
Vol 55 (9) ◽  
pp. 4090-4095 ◽  
Author(s):  
Lingzhi Wang ◽  
Gaik Hong Soon ◽  
Kok-Yong Seng ◽  
Jun Li ◽  
Edmund Lee ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Healthy Volunteers ◽  
Half Life ◽  
Pharmacokinetic Modeling ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Time Curve ◽  
Concentration Time ◽  
Relative Standard ◽  
Intracellular Concentrations

ABSTRACTRaltegravir is a potent inhibitor of HIV integrase. Persistently high intracellular concentrations of raltegravir may explain sustained efficacy despite high pharmacokinetic variability. We performed a pharmacokinetic study of healthy volunteers. Paired blood samples for plasma and peripheral blood mononuclear cells (PBMCs) were collected predose and 4, 8, 12, 24, and 48 h after a single 400-mg dose of raltegravir. Samples of plasma only were collected more frequently. Raltegravir concentrations were determined using liquid chromatography-mass spectrometry. The lower limits of quantitation for plasma and PBMC lysate raltegravir were 2 nmol/liter and 0.225 nmol/liter, respectively. Noncompartmental analyses were performed using WinNonLin. Population pharmacokinetic analysis was performed using NONMEM. Six male subjects were included in the study; their median weight was 67.4 kg, and their median age was 33.5 years. The geometric mean (GM) (95% confidence interval shown in parentheses) maximum concentration of drug (Cmax), area under the concentration-time curve from 0 to 12 h (AUC0–12), and area under the concentration-time curve from 0 h to infinity (AUC0–∞) for raltegravir in plasma were 2,246 (1,175 to 4,294) nM, 10,776 (5,770 to 20,126) nM · h, and 13,119 (7,235 to 23,788) nM · h, respectively. The apparent plasma raltegravir half-life was 7.8 (5.5 to 11.3) h. GM intracellular raltegravirCmax, AUC0–12, and AUC0–∞were 383 (114 to 1,281) nM, 2,073 (683 to 6,290) nM · h, and 2,435 (808 to 7,337) nM · h (95% confidence interval shown in parentheses). The apparent intracellular raltegravir half-life was 4.5 (3.3 to 6.0) h. Intracellular/plasma ratios were stable for each patient without significant time-related trends over 48 h. Population pharmacokinetic modeling yielded an intracellular-to-plasma partitioning ratio of 11.2% with a relative standard error of 35%. The results suggest that there is no intracellular accumulation or persistence of raltegravir in PBMCs.

scholarly journals Pharmacokinetic Parameters of Ciprofloxacin in Bangladeshi Volunteers: A Preliminary Evaluation

2014 ◽  
Vol 27 (1-2) ◽  
pp. 1-8
Author(s):  
Reefat Zaman Chowdhury ◽  
Md Saiful Islam ◽  
Md Sayedur Rahman
Keyword(s):  
Healthy Volunteers ◽  
Oral Route ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Intravenous Route ◽  
Population Pharmacokinetic ◽  
Healthy Male ◽  
Healthy Male Volunteers ◽  
Male Volunteers ◽  
The Difference

The present study has attempted to establish a High-performance liquid chromatography (HPLC) method to determine ciprofloxacin in plasma, in order to evaluate the bioavailability of ciprofloxacin. In this study, initially 8 (eight) Bangladeshi Bangalee healthy male volunteers and 7 (seven) Bangladeshi Tribal healthy male volunteers received 500 mg tablet of pioneer brand of ciprofloxacin in oral route. Blood samples were collected at 0, 30, 60, 120, 180, 360, 540 and 720 minutes after drug administration. After 1 week of washout period, same volunteers of two groups received 200 mg injection of pioneer brand of ciprofloxacin in intravenous route. HPLC with ultraviolet detection was used to quantify plasma ciprofloxacin concentrations. In case of oral route, AUC0–12h, Cmax, Tmax and T1/2 values for Bangladeshi Bangalee and Tribal healthy volunteers were 545.53 ± 32.35 & 655.74 ± 16.57 ?g min/mL, 2.19 ± 0.16 & 2.49 ± 0.20 ?g/mL, 75.00 ± 27.77 & 94.29 ± 32.07 min and 241.96 ± 13.53 & 242.02 ± 19.88 min respectively. In case of intravenous route, the AUC0–12h, Cmax, Tmax and T1/2 values for Bangladeshi Bangalee and Tribal healthy volunteers were 344.07 ± 29.31 & 343.31 ± 25.34 ?g min/mL, 2.47 ± 0.17 & 2.46 ± 0.18 ?g/mL, 30.00 ± 0.00 & 30.0 ± 0.0 min and 278.16 ± 1.74 & 272.74 ± 4.42 min respectively and the difference between these two groups of volunteers was not significant. The difference in AUC0–12h, Cmax, Tmax and T1/2 values between these two groups of volunteers was significant. The mean percent absolute bioavailability in Bangladeshi Bangalee and Tribal healthy volunteers was 64.04 ± 3.21 and 76.81 ± 6.71 respectively. In conclusion, pharmacokinetic parameters of ciprofloxacin significantly varied among Bangladeshi Bangalee and Bangladeshi Tribal healthy volunteers indicating necessity of further study on population pharmacokinetic in these groups of people. DOI: http://dx.doi.org/10.3329/bjpp.v27i1-2.20066 Bangladesh J Physiol Pharmacol 2011;27(1&2):1-8.

scholarly journals Pharmacokinetic Modeling and Dose Selection in a Randomized, Double-Blind, Placebo-Controlled Trial of a Human Recombinant Alkaline Phosphatase in Healthy Volunteers

2016 ◽  
Vol 55 (10) ◽  
pp. 1227-1237 ◽  
Author(s):  
Esther Peters ◽  
Jules A. A. C. Heuberger ◽  
Renger Tiessen ◽  
Andrea van Elsas ◽  
Rosalinde Masereeuw ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Healthy Volunteers ◽  
Controlled Trial ◽  
Pharmacokinetic Modeling ◽  
Dose Selection ◽  
Double Blind ◽  
Double Blind Placebo

scholarly journals Pharmacokinetic parameters of Amoxicillin in Bangladeshi volunteers: a preliminary evaluation

2014 ◽  
Vol 26 (1-2) ◽  
pp. 1-9
Author(s):  
Reefat Zaman Chowdhury ◽  
Md. Saiful Islam ◽  
Md. Sayedur Rahman
Keyword(s):  
Healthy Volunteers ◽  
High Performance ◽  
Oral Route ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Intravenous Route ◽  
Population Pharmacokinetic ◽  
Preliminary Evaluation ◽  
The Difference ◽  
Bangladeshi Population

The present study was designed to get preliminary idea about the pharmacokinetic behavior of the Bangladeshi population through estimating plasma amoxicillin concentration by High-Performance Liquid Chromatography (HPLC) with ultraviolet detection. In this study, Bangladeshi healthy volunteers were divided in two groups, 8 Bangladeshi Bangalee and 7 Bangladeshi Tribal male healthy volunteers. Both the groups received 500 mg of amoxicillin in oral route and blood samples were collected at 0, 30, 60, 120, 180, 360 and 480 minutes after drug administration. After 1 week of washout period, same volunteers of two groups received 500 mg of amoxicillin in intravenous route. In case of oral route, the Cmax, AUC0–8h, Tmax and T1/2 values for Bangladeshi Bangalee and Tribal healthy volunteers were 6.78 ± 1.20 & 9.10 ± 1.34 ìg/mL, 1290.13 ± 158.39 & 1766.06 ± 188.37 ìg min/mL, 82.50 ± 32.05 & 102.86 ± 29.28 min and 96.05 ± 3.80 & 88.15 ± 5.33 min respectively. The difference in Cmax, AUC0–8h and T1/2 values between these two groups of volunteers was significant (p<0.01, p<0.001 and p<0.01 respectively). However, the difference in Tmax was not significant (p>0.05). In case of intravenous route, the C30 min and AUC0–8h values for Bangladeshi Bangalee and Tribal healthy volunteers were 17.88 ± 1.14 & 18.58 ± 0.71 ìg/mL, 2297.96 ± 222.49 & 2376.41 ± 149.99 ìg min/mL respectively and the difference was not significant (p>0.05). The T1/2 for Bangladeshi Bangalee and Tribal healthy volunteers were 97.50 ± 3.33 & 94.40 ± 2.33 min respectively and the difference was significant (p<0.05). The Mean Percent Absolute Bioavailability in Bangladeshi Bangalee and Tribal healthy volunteers was 56.76 ± 5.39 and 74.17 ± 3.90 respectively and the difference was highly significant (p<0.001). The study concluded that the pharmacokinetic parameters of amoxicillin significantly varied among Bangladeshi Bangalee and Bangladeshi Tribal healthy volunteers indicating necessity of further study on population pharmacokinetic to formulate tailor-made drug therapy in these groups of people. http://dx.doi.org/10.3329/bjpp.v26i1-2.19958 Bangladesh J Physiol Pharmacol 2010; 26(1&2) : 1-9

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