The Pharmacokinetics of Etanercept in Healthy Volunteers

2000 ◽  
Vol 34 (2) ◽  
pp. 161-164 ◽  
Author(s):  
Joan M Korth-Bradley ◽  
Abbe Sue Rubin ◽  
Roberta K Hanna ◽  
Donna K Simcoe ◽  
Mary E Lebsack
Keyword(s):  
Healthy Volunteers ◽  
Subcutaneous Injection ◽  
Peak Concentration ◽  
Subcutaneous Administration ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pharmacokinetic Parameters ◽  
Time Data ◽  
Serum Samples ◽  
Drug Concentrations ◽  
Apparent Clearance

OBJECTIVE: To describe the pharmacokinetics of etanercept when administered by subcutaneous injection in single doses to healthy volunteers. METHODS: Twenty-six healthy volunteers between 19 and 50 years of age received single doses of etanercept 25 mg by subcutaneous injection into the abdomen. Serial serum samples were collected for 21 days. An enzyme-linked immunosorbent assay with a quantitation limit of 0.3 ng/mL was used to measure the drug concentrations. RESULTS: Etanercept was well tolerated by healthy volunteers. A one-compartment model was found to best describe the concentration–time data and was used to determine the pharmacokinetic parameters. Etanercept is slowly absorbed from the site of injection with a time of peak concentration (± SD) of 51 ± 14 hours; peak concentration was 1.46 ± 0.72 mg/L. The AUC was 235 ± 98 mg•h/L, apparent clearance was 132 ± 85 mL/h, apparent volume of distribution was 12 ± 6 L, and the half-life was 68 ± 19 hours. CONCLUSIONS: Etanercept was slowly absorbed and slowly eliminated after subcutaneous administration. Dosing at the recommended rate of 25 mg twice weekly would be expected to result in concentrations of approximately 3 mg/L. Intersubject variability for apparent clearance in healthy volunteers was 64%.

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 Detection of Immunoglobulin G and A Antibodies to Rubella Virus in Urine and Antibody Responses to Vaccine-Induced Infection

1998 ◽  
Vol 5 (1) ◽  
pp. 24-27 ◽  
Author(s):  
Shigeo Takahashi ◽  
Fusaichi Machikawa ◽  
Atsunari Noda ◽  
Tetsuya Oda ◽  
Tetsuya Tachikawa
Keyword(s):  
Healthy Volunteers ◽  
Immunoglobulin G ◽  
Rubella Virus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Recent Infection ◽  
Serum Igg ◽  
Assay Methods ◽  
Rubella Vaccination ◽  
Serum Igg Levels

ABSTRACT Urine and serum samples from 89 healthy volunteers and three healthy individuals who underwent rubella vaccination were tested for immunoglobulin G (IgG), IgA, and IgM to rubella virus (RV) by enzyme-linked immunosorbent assay methods. Subjects with positive (n = 68) or negative (n = 21) results for serum IgG were exactly the same as those with the corresponding results for urinary IgG. Both urinary and serum IgG levels remained elevated from the 3rd or 4th week after vaccination until the end of the study. Both urinary IgA and serum IgM levels tended to increase rapidly between the 3rd and 5th week and then gradually decrease until the end of the study, but the levels of both remained positive except for one sample each at the end (26th week). On the other hand, the ratio of anti-RV IgA titer to anti-RV IgG titer in urine (urinary anti-RV IgA/IgG ratio) increased rapidly between the 3rd and 4th week after vaccination and then rapidly returned to the ratio levels of the subjects positive for serum IgG from among the healthy volunteers. In summary, detection of urinary anti-RV IgG should be useful for screening for previous RV infection, and measurement of urinary anti-RV IgA/IgG ratio might be useful for diagnosing recent infection.

scholarly journals Intraocular Pharmacokinetics and Safety of Subretinal Injection Compared with Intravitreal Application of Conbercept in Vitrectomized Rabbit Eyes

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Teng-teng Yao ◽  
Xiao-liang Jin ◽  
Yuan Yang ◽  
Yi-xiao Wang ◽  
Ya-li Zhou ◽  
...  
Keyword(s):  
Intravitreal Injection ◽  
Clearance Rate ◽  
Half Life ◽  
Ocular Tissue ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Functional Changes ◽  
Drug Concentrations ◽  
Subretinal Injection

Purpose. To evaluate the ocular pharmacokinetic properties of subretinal conbercept injection in vitrectomized rabbit eyes and to compare them with those by intravitreal injection. Methods. The following groups of New Zealand white rabbits received conbercept injections (0.5 mg/0.05 ml): a subretinal group (subretinal injection in vitrectomized eyes), an intravitreal group (intravitreal injection in vitrectomized eyes), and a control group (intravitreal injection in nonvitrectomized eyes). Drug concentrations in the aqueous humor (AH), the vitreous humor (VH), and the retina were measured by the enzyme-linked immunosorbent assay (ELISA), and pharmacokinetic parameters were calculated. Ophthalmic B-ultrasonography, electroretinogram (ERG), and hematoxylin and eosin (H&E) staining were performed to evaluate the safety of subretinal injection. Results. On the 28th day after injection, the drug level in the subretinal group was significantly higher than that in the intravitreal group in the AH (0.90 ± 0.25 μg/ml and 0.11 ± 0.07 μg/ml, P<0.001, respectively) and the VH (5.00 ± 3.86 μg/ml and 0.40 ± 0.34 μg/ml, P=0.016, respectively). The clearance rate from AH and VH exhibited terminal half-life times of 9.88 ± 6.48 days and 6.14 ± 1.69 days by the subretinal application, which were significantly longer than the half-life in AH (3.34 ± 0.58 days, P=0.004) and VH (3.12 ± 0.45 days, P=0.002) by the intravitreal application to the vitrectomized eyes. No significant physiological and anatomical functional changes in the retina were observed after subretinal conbercept injection. Conclusions. Our study indicates that applying conbercept by subretinal injection can reduce the drug clearance rate and sustain a long maintenance period in ocular tissue, which suggests that subretinal conbercept injection may be a potentially valuable treatment option.

scholarly journals Disposition and bioavailability of ceftazidime after intraperitoneal administration in patients receiving continuous ambulatory peritoneal dialysis.

1996 ◽  
Vol 7 (11) ◽  
pp. 2399-2402 ◽  
Author(s):  
S Stea ◽  
T Bachelor ◽  
M Cooper ◽  
P de Souza ◽  
K Koenig ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
High Performance ◽  
Intraperitoneal Administration ◽  
Pharmacokinetic Parameters ◽  
Time Data ◽  
Standard Regimen ◽  
Drug Concentrations ◽  
Trough Serum ◽  
Dosing Regimens

This study investigated the disposition and bioavailability of ceftazidime when it was given intraperitoneally. Seven patients were given 1 gm of ceftazidime intravenously, and 1 wk later, the same dose was given intraperitoneally. After both intravenous and intraperitoneal dosing, serum and peritoneal dialysate samples were obtained at set time intervals over a 24-h period. High-performance liquid chromatography was used to determine the ceftazidime concentrations in the serum and dialysate samples. Inspection of the concentration versus time data after intraperitoneal dosing demonstrated that serum ceftazidime concentrations reached therapeutic (> 8 micrograms/mL) levels within 30 min and remained in the therapeutic range for the entire 24-h period. Simulation of a variety of ceftazidime dosing regimens using the mean pharmacokinetic parameters from this population of patients suggests that a regimen of 1.5 gm administered intraperitoneally every 24 h produces trough serum drug concentrations (approximately 40 micrograms/mL) similar to those achieved with a standard regimen of 1.0 gm given intravenously every 24 h in patients undergoing continuous ambulatory peritoneal dialysis. It was concluded that the intraperitoneal dosing of ceftazidime in these patients is an equally effective and a more convenient alternative to its administration.

scholarly journals Pharmacokinetics and Renal Disposition of Polymyxin B in an Animal Model

2012 ◽  
Vol 56 (11) ◽  
pp. 5724-5727 ◽  
Author(s):  
Kamilia Abdelraouf ◽  
Jie He ◽  
Kimberly R. Ledesma ◽  
Ming Hu ◽  
Vincent H. Tam
Keyword(s):  
Renal Insufficiency ◽  
Kidney Tissue ◽  
Polymyxin B ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Serum Samples ◽  
Time Curve ◽  
Renal Disposition ◽  
Drug Concentrations ◽  
Serial Serum

ABSTRACTThe increasing prevalence of multidrug-resistant Gram-negative infections has led to the resurgence of systemic polymyxin B, but little is known about its pharmacokinetics. The objective of this study was to characterize the pharmacokinetics and renal disposition of polymyxin B. Eight female Sprague-Dawley rats (weight, 225 to 250 g) were administered a single intravenous polymyxin B dose (4 mg/kg of body weight). Serial serum samples were collected and assayed for major polymyxin B components using a validated ultraperformance liquid chromatography-tandem mass spectrometry method. The best-fit pharmacokinetic parameters of each component were derived and compared using one-way analysis of variance. Cumulative urine was also collected daily for 48 h and assayed for polymyxin B. Kidney drug concentrations were measured at 6 h (n= 3) and 48 h (n= 3) after the same dose. Additionally, three rats were administered 2 doses of intravenous polymyxin B (4 mg/kg) 7 days apart. Serial serum samples were collected pre- and post-renal insufficiency (induced by uranyl nitrate) and assayed for polymyxin B. The pharmacokinetic parameters of the major components did not appear to be significantly different (P> 0.05). Less than 1% of the dose was recovered unchanged in urine collected over 48 h following administration. Therapeutic drug concentrations persisted in kidney tissue at 48 h. The post-renal insufficiency to pre-renal insufficiency ratio of the area under the serum concentration-time curve from time zero to infinity was 1.33 ± 0.04. Polymyxin B components appear to have similar pharmacokinetics. Polymyxin B preferentially persists in kidneys, which suggests a selective uptake process in renal cells. A mechanism(s) other than renal excretion could be involved in polymyxin B elimination, and dosing adjustment in renal insufficiency may not be necessary.

scholarly journals Pharmacokinetics and Immunogenicity of Frunevetmab in Osteoarthritic Cats Following Intravenous and Subcutaneous Administration

2021 ◽  
Vol 8 ◽  
Author(s):  
Rodney R. Walters ◽  
Joseph F. Boucher ◽  
Flavia De Toni
Keyword(s):  
Drug Exposure ◽  
Subcutaneous Administration ◽  
Field Studies ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Time Data ◽  
Drug Levels ◽  
Trough Concentrations

Osteoarthritis and other degenerative joint diseases are common causes of chronic pain in cats. Frunevetmab is a felinized monoclonal antibody that binds to nerve growth factor (NGF) and provides relief from pain by blocking the receptor-mediated signaling cascade induced by NGF. Results from three studies were combined to provide an overview of frunevetmab pharmacokinetics (PK) and immunogenicity. The objective of the first study was to establish the pharmacokinetic parameters resulting from intravenous (IV) and subcutaneous (SC) administration of frunevetmab to the feline patient population at 3 mg/kg. Ten adult cats with naturally-occurring osteoarthritis were administered frunevetmab in a crossover design at 28 day intervals. Non-compartmental pharmacokinetic analysis of the plasma concentration-time data showed that the half-life was 10.1 ± 1.9 days after IV dosing and the SC bioavailability was 60.3 ± 15.8% with maximum drug levels observed at 3–7 days after dosing. Plasma samples were collected at ~28 days after dosing during two field safety and effectiveness studies of cats with degenerative joint disease. The doses ranged from 1.0 to 2.8 mg/kg; 2 or 3 doses were administered either SC/IV, SC/SC, or SC/SC/SC. The data from these studies along with the data from the laboratory pharmacokinetic study were analyzed using non-linear mixed-effects (NLME) modeling. The model closely predicted the trough concentrations from the two field studies, including the IV treatment in the pilot field study. The trough concentrations were predicted to be close to steady-state after 2 doses. A second objective was to determine the incidence and clinical relevance of frunevetmab immunogenicity. A three-tier anti-drug antibody assay (screen, confirm, titer) was developed and validated. Immunogenicity was assessed in 259 frunevetmab-treated animals enrolled in the two field studies. Only 4 of these animals (1.5%) appeared to develop immunogenicity to frunevetmab. None of the four exhibited adverse events attributed to immunogenicity and no impact on drug levels or efficacy was observed in three of the animals. In the placebo animals, 2.3% (3/131) appeared to develop treatment-emergent immunogenicity. Overall, frunevetmab administration resulted in a very low incidence of treatment-emergent immunogenicity with no safety findings and minimal effect on drug exposure and efficacy.

scholarly journals ELISA Development for Serum Hemeoxygenase-1 and Its Application to Patients with Acute Respiratory Distress Syndrome

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Yu Hara ◽  
Masaharu Shinkai ◽  
Masataka Taguri ◽  
Kenjiro Nagai ◽  
Satoru Hashimoto ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Healthy Volunteers ◽  
Distress Syndrome ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Disease Prognosis ◽  
Essential Enzyme ◽  
Higher Sensitivity

Background. Hemeoxygenase-1 (HO-1) is an essential enzyme in heme catabolism and has been proposed as a biomarker of lung disease prognosis. We modified a commercial HO-1 enzyme-linked immunosorbent assay (ELISA) kit to achieve higher sensitivity and evaluated if serum HO-1 could be a biomarker to predict the prognosis of acute respiratory distress syndrome (ARDS) patients.Methods. Serum samples were collected from 15 healthy volunteers to validate the modified ELISA. In the 22 patients with ARDS who were enrolled, serum HO-1 was measured upon diagnosis (D0) and at 7 days after diagnosis (D7).Results. The serum HO-1 concentration could be measured in all healthy volunteers. The intra- and interassay tests and the percentage recovery test were acceptable. Compared with normal control subjects, patients with ARDS had significantly higher D0 HO-1 concentrations (75.4 ng/mL versus 31.7 ng/mL,P<0.001). The 28-day survival was significantly better in patients with low D0 HO-1 (<75.8 ng/mL) than in those with high D0 HO-1 (≥75.8 ng/mL) (mortality rate: 18% versus 73%,P=0.016). Nonsurvivors had significantly higher D0 and D7 HO-1 concentrations than survivors (P<0.05).Conclusion. Serum HO-1 may be a useful biomarker to predict the prognosis of patients with ARDS.

scholarly journals Evaluation of Drug-Drug Interactions between Direct-Acting Anti-Hepatitis C Virus Combination Regimens and the HIV-1 Antiretroviral Agents Raltegravir, Tenofovir, Emtricitabine, Efavirenz, and Rilpivirine

2016 ◽  
Vol 60 (5) ◽  
pp. 2965-2971 ◽  
Author(s):  
Amit Khatri ◽  
Sandeep Dutta ◽  
Martin Dunbar ◽  
Thomas Podsadecki ◽  
Roger Trinh ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Drug Interactions ◽  
Healthy Volunteers ◽  
Antiretroviral Drugs ◽  
Pharmacokinetic Parameters ◽  
Direct Acting Antiviral ◽  
Drug Concentrations ◽  
Tenofovir Df ◽  
Direct Acting

ABSTRACTThe three direct-acting antiviral agent (3D) regimen is a novel combination of direct-acting antiviral agents (DAAs) that has proven effective for the treatment of hepatitis C virus (HCV) infection. Given the potential for coadministration in patients with human immunodeficiency virus infection, possible drug interactions with antiretroviral drugs must be carefully considered. Four phase 1, multiple-dose pharmacokinetic studies were conducted in healthy volunteers (n= 66). The 3D regimen of 150/100 mg daily paritaprevir/ritonavir, 25 mg daily ombitasvir, and 400 mg twice-daily dasabuvir was administered alone or in combination with 200 mg daily of emtricitabine and 300 mg daily of tenofovir disoproxil fumarate (tenofovir DF), 25 mg daily of rilpivirine, or 400 mg of raltegravir twice daily. A 2-DAA regimen of 150/100 mg daily paritaprevir/ritonavir and 400 mg of dasabuvir twice daily was also studied in combination with efavirenz/emtricitabine/tenofovir DF at 600/200/300 mg daily, respectively (Atripla; Bristol-Myers Squibb). Pharmacokinetic parameters were determined from plasma drug concentrations. No clinically significant drug interactions were observed (≤32% change in exposure) between the 3D regimen and that of emtricitabine plus tenofovir DF. Raltegravir exposure was increased up to 134% when the drug was coadministered with the 3D regimen. Although coadministration with rilpivirine was well tolerated in healthy volunteers, observed elevations in rilpivirine exposures may increase the potential for adverse drug reactions. Concomitant use of the 2-DAA regimen and efavirenz/emtricitabine/tenofovir DF was discontinued owing to poor tolerability and adverse events. No dose adjustment is required during coadministration of raltegravir, tenofovir DF, or emtricitabine with the 3D regimen. Rilpivirine is not recommended and efavirenz is contraindicated for coadministration with the 3D regimen.

TBE in Sweden

2020 ◽  
Keyword(s):  
Genetic Characterization ◽  
Immunoglobulin M ◽  
Enzyme Linked Immunosorbent Assay ◽  
Second Phase ◽  
Serum Samples ◽  
Tick Borne Encephalitis ◽  
Specific Immunoglobulin ◽  
Tick Borne Encephalitis Virus ◽  
First Time

Tick-borne encephalitis virus (TBEV) was isolated for the first time in Sweden in 1958 (from ticks and from 1 tick-borne encephalitis [TBE] patient).1 In 2003, Haglund and colleagues reported the isolation and antigenic and genetic characterization of 14 TBEV strains from Swedish patients (samples collected 1991–1994).2 The first serum sample, from which TBEV was isolated, was obtained 2–10 days after onset of disease and found to be negative for anti-TBEV immunoglobulin M (IgM) by enzyme-linked immunosorbent assay (ELISA), whereas TBEV-specific IgM (and TBEV-specific immunoglobulin G/cerebrospinal fluid [IgG/CSF] activity) was demonstrated in later serum samples taken during the second phase of the disease.

scholarly journals Pestivirus infections in cervids from the Czech Republic

2009 ◽  
Vol 54 (No. 4) ◽  
pp. 191-193
Author(s):  
K. Sedlak ◽  
T. Girma ◽  
J. Holejsovsky
Keyword(s):  
Czech Republic ◽  
Cervus Elaphus ◽  
Red Deer ◽  
Competitive Inhibition ◽  
Enzyme Linked Immunosorbent Assay ◽  
Border Disease Virus ◽  
Serum Samples ◽  
The Czech Republic ◽  
Diarrhea Virus ◽  
Border Disease

372 sera of cervids from the Czech Republic were examined for antibodies to the bovine viral diarrhea virus (BVDV) and border disease virus (BDV) by competitive-inhibition enzyme-linked immunosorbent assay (ELISA), and for the presence of the BVDV by AgELISA. Antibodies to BVDV/BDV were found in 0.6% (two positive/305 tested) red deer (<I>Cervus elaphus</I>). BVDV/BDV antibodies were not found in four sika deer (<I>Cervus Nippon</I>) and 63 fallow deer (<I>Dama dama</I>). All serum samples were BVDV antigen negative. Our results confirmed that red deer in the Czech Republic are only rarely infected with Pestiviruses. This was the first survey of pestiviruses in farmed and wild cervids in the Czech Republic.

Sign in / Sign up

Export Citation Format

Share Document