Relationship Between Apparent Systemic Clearance of Vemurafenib and Toxicity in Patients with Melanoma

2021 ◽  
Author(s):  
Ganessan Kichenadasse ◽  
Jim Henry Hughes ◽  
Alia Fahmy ◽  
Andrew Rowland ◽  
Michael J. Sorich ◽  
...  
Keyword(s):  
Systemic Clearance

Pharmacokinetics of Propofol after a Single Dose in Children Aged 1–3 Years with Minor Burns

1996 ◽  
Vol 84 (3) ◽  
pp. 526-532 ◽  
Author(s):  
I. Murat ◽  
V. Billard ◽  
J. Vernois ◽  
M. Zaouter ◽  
P. Marsol ◽  
...  
Keyword(s):  
Single Dose ◽  
Surface Area ◽  
Total Body Surface Area ◽  
Central Compartment ◽  
Pharmacokinetic Parameters ◽  
Systemic Clearance ◽  
Older Children ◽  
Noncompartmental Analysis ◽  
Two Stage ◽  
Stage Analysis

Background No complete pharmacokinetic profile of propofol is yet available in children younger than 3 yr, whereas clinical studies have demonstrated that both induction and maintenance doses of propofol are increased with respect to body weight in this age group compared to older children and adults. This study was therefore undertaken to determine the pharmacokinetics of propofol after administration of a single dose in aged children 1-3 yr requiring anesthesia for dressing change. Methods This study was performed in 12 children admitted to the burn unit and in whom burn surface area was less than or equal to 12% of total body surface area. Exclusion criteria were: unstable hemodynamic condition, inappropriate fluid loading, associated pulmonary injury, or burn injury older than 2 days. Propofol (4 mg.kg(-1))plus fentanyl (2.5 microg.kg(-1)) was administered while the children were bathed and the burn area cleaned during which the children breathed spontaneously a mixture of oxygen and nitrous oxide (50:50). Venous blood samples of 300 microl were obtained at 5, 15, 30, 60, 90, and 120 min, and 3, 4, 8, and 12 thereafter injection; an earlier sample was obtained from 8 of 12 children. The blood concentration curves obtained for individual children were analyzed by three different methods: noncompartmental analysis, mixed effects population model, and standard two-stage analysis. Results Using noncompartmental analysis, total clearance of propofol (+/-SD) was 0.053+/-0.013l.kg(-1).min(-1), volume of distribution at steady state9.5 +/- 3.7l.kg(-1),and residence time 188 +/- 85 min. Propofol pharmacokinetics were best described by a weight-proportional three-compartmental model in both population and two-stage analysis. Estimated and derived pharmacokinetic parameters were similar using these two pharmacokinetic approaches. Results of population versus two-stage analysis are as follow: systemic clearance 0.049 versus 0.048 l.kg(-).min(-1), volume of central compartment 1.03 versus 0.95 l.kg(-1), volume of steady state 8.09 versus 8.17 l.kg(-1). Conclusions The volume of the central compartment and the systemic clearance were both greater than all values reported in older children and adults. This is consistent with the increased propofol requirements for both induction and maintenance of anesthesia in children 1-3 yr. (Key words: Anesthesia: pediatric. Pharmacokinetics: propofol.)

Pharmacokinetic Studies of Propoxyphene IV: Effect of Renal Failure on Systemic Clearance in Rats

1980 ◽  
Vol 69 (3) ◽  
pp. 363-364 ◽  
Author(s):  
Stephen M. Roberts ◽  
Gerhard Levy
Keyword(s):  
Renal Failure ◽  
Pharmacokinetic Studies ◽  
Systemic Clearance

scholarly journals Pharmacokinetics and Pharmacodynamics of Imipenem during Continuous Renal Replacement Therapy in Critically Ill Patients

2005 ◽  
Vol 49 (6) ◽  
pp. 2421-2428 ◽  
Author(s):  
Douglas N. Fish ◽  
Isaac Teitelbaum ◽  
Edward Abraham
Keyword(s):  
High Performance ◽  
Continuous Venovenous Hemofiltration ◽  
Systemic Clearance ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Drug Infusion ◽  
Dosing Interval ◽  
Adult Intensive Care Unit ◽  
Drug Concentrations ◽  
Elimination Half ◽  
Higher Doses

ABSTRACT The pharmacokinetics of imipenem were studied in adult intensive care unit (ICU) patients during continuous venovenous hemofiltration (CVVH; n = 6 patients) or hemodiafiltration (CVVHDF; n = 6 patients). Patients (mean ± standard deviation age, 50.9 ± 15.9 years; weight, 98.5 ± 15.9 kg) received imipenem at 0.5 g every 8 to 12 h (total daily doses of 1 to 1.5 g/day) by intravenous infusion over 30 min. Pre- and postmembrane blood (plasma) and corresponding ultrafiltrate or dialysate samples were collected 1, 2, 4, and 8 or 12 h (depending on dosing interval) after completion of the drug infusion. Drug concentrations were measured using validated high-performance liquid chromatography methods. Mean systemic clearance (CL S ) and elimination half-life (t 1/2) of imipenem were 145 ± 18 ml/min and 2.7 ± 1.3 h during CVVH versus 178 ± 18 ml/min and 2.6 ± 1.6 h during CVVHDF, respectively. Imipenem clearance was substantially increased during both CVVH and CVVHDF, with membrane clearance representing 25% and 32% of CL S , respectively. The results of this study indicate that CVVH and CVVHDF contribute to imipenem clearance to a greater degree than previously reported. Imipenem doses of 1.0 g/day appear to achieve concentrations adequate to treat most common gram-negative pathogens (MIC up to 2 μg/ml) during CVVH or CVVHDF, but doses of 2.0 g/day or more may be required to adequately treat and prevent resistance in pathogens with higher MICs (MIC = 4 to 8 μg/ml). Higher doses should only be used after consideration of potential central nervous system toxicities or other risks of therapy in these severely ill patients.

SIGN-R1 and complement factors are involved in the systemic clearance of radiation-induced apoptotic cells in whole-body irradiated mice

2015 ◽  
Vol 463 (4) ◽  
pp. 1064-1070 ◽  
Author(s):  
Jin-Yeon Park ◽  
SoHee Loh ◽  
Eun-hee Cho ◽  
Hyeong-Jwa Choi ◽  
Tae-Young Na ◽  
...  
Keyword(s):  
Whole Body ◽  
Apoptotic Cells ◽  
Systemic Clearance ◽  
Complement Factors ◽  
Radiation Induced

Argatroban and Renal Replacement Therapy in Patients with Heparin-Induced Thrombocytopenia

2005 ◽  
Vol 39 (2) ◽  
pp. 231-236 ◽  
Author(s):  
Ignatius Y Tang ◽  
Donna S Cox ◽  
Kruti Patel ◽  
Bharathi V Reddy ◽  
Linda Nahlik ◽  
...  
Keyword(s):  
At Risk ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Systemic Clearance ◽  
Recovery Method ◽  
P Values ◽  
Heparin Induced Thrombocytopenia ◽  
Alternative Anticoagulation

BACKGROUND: Argatroban, a direct thrombin inhibitor, is an effective anticoagulant for patients who have heparin-induced thrombocytopenia (HIT). Anticoagulation is usually required for renal replacement therapy (RRT). OBJECTIVE: To prospectively evaluate the pharmacokinetics, pharmacodynamics, and safety of argatroban during RRT in hospitalized patients with or at risk for HIT. METHODS: Five patients with known or suspected HIT underwent hemodialysis (n = 4) or continuous venovenous hemofiltration (CVVH, n = 1), while receiving a continuous infusion of argatroban 0.5–2 μg/kg/min. Activated partial thromboplastin times (aPTTs), activated clotting times (ACTs), argatroban concentrations (plasma, dialysate, CVVH effluent), and safety were assessed before, during, and after a 4-hour session of RRT. Systemic and dialytic argatroban clearances were calculated. RESULTS: Among the 4 hemodialysis patients, aPTT, ACT, and plasma argatroban concentrations remained stable during RRT, with respective mean ± SD values of 74.3 ± 34.2 seconds, 198 ± 23 seconds, and 499 ± 353 ng/mL before RRT, and 70.6 ± 21.4 seconds, 181 ± 12 seconds, and 453 ± 295 ng/mL 2 hours after starting RRT (p values NS). Systemic clearance was 17.7 ± 12.8 L/h before hemodialysis and 17.0 ± 9.5 L/h during hemodialysis (n = 2). The dialyzer clearance (dialysate recovery method) was 1.5 ± 0.4 L/h (n = 4). Generally similar responses occurred in the CVVH patient: systemic argatroban clearance was 4.8 L/h before CVVH and 4 L/h during CVVH. The hemofilter argatroban clearance was 0.9 L/h. No bleeding or thrombosis occurred. CONCLUSIONS: Argatroban provides effective alternative anticoagulation in patients with or at risk for HIT during RRT. Argatroban clearance by high-flux membranes during hemodialysis and CVVH is clinically insignificant, necessitating no dose adjustment.

Synthesis and Pharmacological Characterization of Novel Glucagon-like Peptide-2 (GLP-2) Analogues with Low Systemic Clearance

2016 ◽  
Vol 59 (7) ◽  
pp. 3129-3139 ◽  
Author(s):  
Kazimierz Wiśniewski ◽  
Javier Sueiras-Diaz ◽  
Guangcheng Jiang ◽  
Robert Galyean ◽  
Mark Lu ◽  
...  
Keyword(s):  
Systemic Clearance ◽  
Pharmacological Characterization ◽  
Glucagon Like Peptide

Systemic Clearance

2008 ◽  
pp. 2892-2892
Keyword(s):  
Systemic Clearance

A phase I clinical and pharmacokinetic study of carboplatin and autologous bone marrow support.

1989 ◽  
Vol 7 (5) ◽  
pp. 651-661 ◽  
Author(s):  
T C Shea ◽  
M Flaherty ◽  
A Elias ◽  
J P Eder ◽  
K Antman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase I ◽  
Autologous Bone Marrow ◽  
Recurrent Ovarian Cancer ◽  
Maximum Tolerated Dose ◽  
Pharmacokinetic Studies ◽  
Systemic Clearance ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Autologous Bone

A series of 33 patients were treated with a four-day continuous infusion of carboplatin in a phase I study to determine the maximum-tolerated dose (MTD) of this agent when used with autologous bone marrow reinfusion. Doses were escalated from 375 to 2,400 mg/m2; autologous bone marrow reinfusion was added to the regimen at doses of 1,600 mg/m2 and above. The MTD was determined to be 2,000 mg/m2. Dose-limiting toxicity consisting of reversible hepatotoxicity, renal dysfunction, and moderate to severe ototoxicity was observed with a dose of 2,400 mg/m2. There were ten responses in 31 heavily pretreated patients, including six responses in 11 patients with recurrent ovarian cancer. Pharmacokinetic studies revealed a systemic clearance (Clss) of 4.5 L/m2/h. This value is consistent with clearances reported for carboplatin administered at lower doses and by different schedules. No evidence for saturation of systemic clearance at higher doses was observed. Carboplatin appears to be an active drug that can undergo considerable dose escalation when used in conjunction with autologous bone marrow support.

Erythromycin attenuates systemic clearance of lidocaine

2003 ◽  
Vol &NA; (1376) ◽  
pp. 15
Author(s):  
&NA;
Keyword(s):  
Systemic Clearance
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