Relationships between steady-state and single-dose plasma drug concentrations for pharmacokinetic systems with nonlinear elimination

1989 ◽  
Vol 10 (5) ◽  
pp. 513-528 ◽  
Author(s):  
Haiyung Cheng ◽  
William J. Jusko
Keyword(s):  
Single Dose ◽  
Steady State ◽  
Plasma Drug ◽  
Drug Concentrations ◽  
Nonlinear Elimination ◽  
Plasma Drug Concentrations

scholarly journals Single- and Multiple-Dose Pharmacokinetics of Caspofungin in Healthy Men

2002 ◽  
Vol 46 (3) ◽  
pp. 739-745 ◽  
Author(s):  
Julie A. Stone ◽  
Sherry D. Holland ◽  
Peter J. Wickersham ◽  
Andrew Sterrett ◽  
Michael Schwartz ◽  
...  
Keyword(s):  
Single Dose ◽  
Multiple Dose ◽  
Panel Study ◽  
Loading Dose ◽  
Plasma Drug ◽  
Single Dose Study ◽  
Healthy Men ◽  
Drug Concentrations ◽  
Multiple Dose Pharmacokinetics ◽  
Plasma Drug Concentrations

ABSTRACT Caspofungin, a glucan synthesis inhibitor, is being developed as a parenteral antifungal agent. The pharmacokinetics of caspofungin following 1-h intravenous infusions in healthy men was investigated in four phase I studies. In an alternating two-panel (six men each), rising-single-dose study, plasma drug concentrations increased proportionally with the dose following infusions of 5 to 100 mg. The β-phase half-life was 9 to 10 h. The plasma drug clearance rate averaged 10 to 12 ml/min. Renal clearance of unchanged drug was a minor pathway of elimination (∼2% of the dose). Multiple-dose pharmacokinetics were investigated in a 2-week, serial-panel (5 or 6 men per panel) study of doses of 15, 35, and 70 mg administered daily; a 3-week, single-panel (10 men) study of a dose of 70 mg administered daily; and a parallel panel study (8 men) of a dose of 50 mg administered daily with or without a 70-mg loading dose on day 1. Moderate accumulation was observed with daily dosing. The degree of drug accumulation and the time to steady state were somewhat dose dependent. Accumulation averaged 24% at 15 mg daily and ∼50% at 50 and 70 mg daily. Mean plasma drug concentrations were maintained above 1.0 μg/ml, a target selected to exceed the MIC at which 90% of the isolates of the most clinically relevant species of Candida were inhibited, throughout therapy with daily treatments of 70 or 50 mg plus the loading dose, while they fell below the target for the first 2 days of a daily treatment of 50 mg without the loading dose. Caspofungin infused intravenously as a single dose or as multiple doses was generally well tolerated. In conclusion, the pharmacokinetics of caspofungin supports the clinical evaluation of once-daily dosing regimens for efficacy against fungal infections.

MATERNAL AND FETAL UPTAKE OF BUPIVACAINE vs. LIDOCAINE AT STEADY STATE PLASMA DRUG CONCENTRATIONS

1987 ◽  
Vol 67 (3) ◽  
pp. A437-A437
Author(s):  
H. O. Morishima ◽  
H. Pedersen ◽  
A. Santos ◽  
M. Finster ◽  
B. G. Covino
Keyword(s):  
Steady State ◽  
Plasma Drug ◽  
Drug Concentrations ◽  
Fetal Uptake ◽  
Plasma Drug Concentrations ◽  
State Plasma

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
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