scholarly journals The impact of MK-467 on plasma drug concentrations, sedation and cardiopulmonary changes in sheep treated with intramuscular medetomidine and atipamezole for reversal

2018 ◽  
Vol 41 (3) ◽  
pp. 447-456 ◽  
Author(s):  
M. Adam ◽  
M. R. Raekallio ◽  
T. Keskitalo ◽  
J. M. Honkavaara ◽  
M. Scheinin ◽  
...  
Keyword(s):  
Plasma Drug ◽  
Drug Concentrations ◽  
The Impact ◽  
Plasma Drug Concentrations

scholarly journals Biopharmaceutical Characterization of Nebulized Antimicrobial Agents in Rats: 1. Ciprofloxacin, Moxifloxacin, and Grepafloxacin

2014 ◽  
Vol 58 (7) ◽  
pp. 3942-3949 ◽  
Author(s):  
Aline Vidal Lacerda Gontijo ◽  
Julien Brillault ◽  
Nicolas Grégoire ◽  
Isabelle Lamarche ◽  
Patrice Gobin ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
Antimicrobial Agents ◽  
Transport Systems ◽  
Systemic Absorption ◽  
Plasma Drug ◽  
Aerosol Delivery ◽  
Active Efflux ◽  
Drug Concentrations ◽  
The Impact ◽  
Plasma Drug Concentrations

ABSTRACTThe aim of this study was to evaluate the biopharmaceutical characteristics of three fluoroquinolones (FQs), ciprofloxacin (CIP), moxifloxacin (MXF), and grepafloxacin (GRX), after delivery via a nebulized aerosol to rats. Bronchoalveolar lavages (BAL) were conducted 0.5, 2, 4, and 6 h after FQ intravenous administration and nebulized aerosol delivery to estimate epithelial lining fluid (ELF) drug concentrations. Plasma drug concentrations were also measured, and profiles of drug concentrations versus time after intravenous administration and nebulized aerosol delivery were virtually superimposable, attesting for rapid and complete systemic absorption of FQs. ELF drug concentrations were systematically higher than corresponding plasma drug concentrations, whatever the route of administration, and average ELF-to-unbound plasma drug concentration ratios post-distribution equilibrium did not change significantly between the ways of administration and were equal: 4.0 ± 5.3 for CIP, 12.6 ± 7.3 for MXF, and 19.1 ± 10.5 for GRX (means ± standard deviations). The impact of macrophage lysis on estimated ELF drug concentrations was significant for GRX but reduced for MXF and CIP; therefore, simultaneous pharmacokinetic modeling of plasma and ELF drug concentrations was only performed for the latter two drugs. The model was characterized by a fixed volume of ELF (VELF), passive diffusion clearance (QELF), and active efflux clearance (CLout) between plasma and ELF, indicating active efflux transport systems. In conclusion, this study demonstrates that ELF drug concentrations of these three FQs are several times higher than plasma drug concentrations, probably due to the presence of efflux transporters at the pulmonary barrier level, but no biopharmaceutical advantage of FQ nebulization was observed compared with intravenous administration.

scholarly journals Impact of hepatitis C and liver fibrosis on antiretroviral plasma drug concentrations in HIV-HCV co-infected patients: the HEPADOSE study

2010 ◽  
Vol 65 (11) ◽  
pp. 2445-2449 ◽  
Author(s):  
S. Dominguez ◽  
J. Ghosn ◽  
G. Peytavin ◽  
M. Guiguet ◽  
R. Tubiana ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Liver Fibrosis ◽  
Plasma Drug ◽  
Drug Concentrations ◽  
Plasma Drug Concentrations

scholarly journals Drug plasma trough concentrations during treatment with daclatasvir and sofosbuvir are associated respectively with liver impairment and with renal dysfunction in HIV/HCV co-infected patients

2019 ◽  
Author(s):  
Ilaria Mastrorosa ◽  
Massimo Tempestilli ◽  
Stefania Notari ◽  
Patrizia Lorenzini ◽  
Gabriele Fabbri ◽  
...  
Keyword(s):  
Renal Dysfunction ◽  
Virologic Response ◽  
Patient Treatment ◽  
Limited Information ◽  
Plasma Drug ◽  
Related Factors ◽  
Immunological Parameters ◽  
Liver Impairment ◽  
Drug Concentrations ◽  
Plasma Drug Concentrations

Abstract Background Sofosbuvir (SOF) plus daclatasvir (DCV) achieved high rates of sustained virologic response (SVR) with no difference according to HIV serostatus. Only limited information is available on the pharmacokinetics variability of SOF and DCV in HIV/HCV co-infected patients. Aim was to evaluate the association of plasma drug concentrations (Ctrough) of SOF and of DCV with patient-, treatment-, and disease-related factors in the real-world setting of HIV/HCV co-infected persons. Methods HIV/HCV co-infected patients, undergoing SOF plus DCV treatment, were prospectively enrolled. At baseline, week4 (W4), end of treatment (EOT), and after-EOT, biochemical and viro-immunological parameters were assessed. FIB-4 score and CKD-EPI equation were used for estimation of liver disease and glomerular filtration rate (eGFR), respectively. SOF, SOF metabolite (GS-331007), and DCV Ctrough were measured at W4 and week8 (W8), and the mean value (mean-Ctrough) was calculated Results Thirty-five patients were included (SVR 94%). Increasing GS-331007 mean-Ctrough significantly correlated with decreasing eGFR at W4 (rho=-0.36; p=0.037) and EOT (rho=-0.34; p=0.048). Between DCV mean-Ctrough and FIB-4, a significant correlation was observed at all time-points: baseline (rho=-0.35; p=0.037), W4 (rho=-0.44; p=0.008), EOT (rho=-0.40; p=0.023), after-EOT (rho=-0.39; p=0.028). Conclusion In HIV/HCV co-infected patients receiving SOF plus DCV, plasma drug concentrations are associated with renal dysfunction for GS-331007 and with liver impairment for DCV. Though clinical and therapeutically relevance of these findings may apparently be limited, growth of clinicians’ knowledge on DAA exposure in difficult-to-treat patients, as cirrhotic and renal impaired subjects, can be relevant in single cases.

Fundamentals of Pharmacokinetics to Assess the Correlation Between Plasma Drug Concentrations and Different Blood Sampling Methods

2019 ◽  
Vol 36 (2) ◽  
Author(s):  
Wei-Ching Chen ◽  
Pei-Wei Huang ◽  
Wan-Ling Yang ◽  
Yen-Lun Chen ◽  
Ying-Ning Shih ◽  
...  
Keyword(s):  
Sampling Methods ◽  
Blood Sampling ◽  
Plasma Drug ◽  
Drug Concentrations ◽  
Plasma Drug Concentrations

Plasma drug concentrations and clinical effects of a peripheral alpha-2-adrenoceptor antagonist, MK-467, in horses sedated with detomidine

2013 ◽  
Vol 40 (3) ◽  
pp. 257-264 ◽  
Author(s):  
Mari H Vainionpää ◽  
Marja R Raekallio ◽  
Soile AE Pakkanen ◽  
Ville Ranta-Panula ◽  
Valtteri M Rinne ◽  
...  
Keyword(s):  
Clinical Effects ◽  
Plasma Drug ◽  
Adrenoceptor Antagonist ◽  
Drug Concentrations ◽  
Plasma Drug Concentrations

scholarly journals Population Pharmacokinetics of Oseltamivir: Pediatrics through Geriatrics

2013 ◽  
Vol 57 (8) ◽  
pp. 3470-3477 ◽  
Author(s):  
Mohamed A. Kamal ◽  
Scott A. Van Wart ◽  
Craig R. Rayner ◽  
Vishak Subramoney ◽  
Daniel K. Reynolds ◽  
...  
Keyword(s):  
Steady State ◽  
Time Course ◽  
Demographic Data ◽  
Visual Predictive Check ◽  
Compartment Model ◽  
Plasma Drug ◽  
First Order ◽  
Drug Concentrations ◽  
Population Pk ◽  
The Impact

ABSTRACTOseltamivir is a potent inhibitor of influenza virus neuraminidase enzymes essential for viral replication. This study aimed to investigate the impact of covariates on pharmacokinetic (PK) variability of oseltamivir and its active metabolite form, oseltamivir carboxylate (OC). Dosing history, plasma drug concentrations, and demographic information were pooled from 13 clinical trials providing data for 390 healthy and infected subjects ranging in age from 1 to 78 years and given oseltamivir doses of 20 to 1,000 mg. Candidate population PK models simultaneously characterizing the time course of oseltamivir and OC in plasma were evaluated by using the NONMEM software program, and subject covariates were assessed using stepwise forward selection (α = 0.01) and backward elimination (α = 0.001). A two-compartment model with first-order absorption of oseltamivir and first-order conversion of oseltamivir to OC and a one-compartment model with first-order elimination of OC were utilized. Body weight when evaluated using a power function was a significant predictor of the apparent oseltamivir clearance and both apparent OC clearance (CLm/F) and central volume of distribution (Vcm/F). Creatinine clearance was a significant predictor of CLm/F, while Vcm/F also decreased linearly with age. A visual predictive check indicated that the final model described oseltamivir and OC concentrations in plasma adequately across dose regimens and subject covariate ranges. Concordance of population mean and individualpost hocpredictions of maximum concentration of drug at steady state (Cmax) and area under the plasma drug concentration-time curve from 0 to 24 h at steady state (AUC0–24) was high (r2= 0.81 and 0.71, respectively). In conclusion, a comprehensive population PK model was constructed to bridge the adult to pediatric oseltamivir PK data, allowing for reasonable estimation of the PK of OC using subject demographic data alone.

Opiate-induced Rhabdomyolysis

1985 ◽  
Vol 4 (1) ◽  
pp. 71-74 ◽  
Author(s):  
P.G. Blain ◽  
R.J.M. Lane ◽  
D.N. Bateman ◽  
M.D. Rawlins
Keyword(s):  
Renal Failure ◽  
Creatine Kinase ◽  
Acute Renal Failure ◽  
Clinical Evidence ◽  
Elevated Serum ◽  
Plasma Drug ◽  
Drug Concentrations ◽  
Serum Aspartate Aminotransferase ◽  
Plasma Drug Concentrations ◽  
Serum Myoglobin

Three patients with opiate self-poisoning developed acute muscle damage with elevated serum aspartate aminotransferase and creatine kinase activities, increased serum myoglobin concentrations, raised plasma creatinine concentrations, hypocalcaemia and hyperphosphataemia. These abnormalities gradually resolved over 7-10 days, but recovery was complicated due to the development of acute renal failure (requiring haemodialysis) in one patient. Plasma drug concentrations, shortly after admission, in the patients taking dihydrocodeine and morphine were grossly elevated (184 and 60 μg/l respectively). Clinical evidence of myopathy was minimal in all three patients and muscle biopsy of one patient was normal at 7 days.

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