Biomedical subjects

Hartmut Derendorf

Publications and source records attributed to Hartmut Derendorf.

60 records · Page 4Linked to original sources

PubMedDate not supplied

Tissue penetration of cefpodoxime into the skeletal muscle and lung in rats.

PURPOSE: The aim of this study was to investigate the pharmacokinetics of cefpodoxime in interstitial tissue fluids (skeletal muscle and lung) in rats by microdialysis, and to examine the relationship between free drug levels in plasma and in tissues. METHODS: Cefpodoxime was administered to anesthetized male Wistar rats as single intravenous bolus of 10 or 20 mg/kg and constant infusion of 260 microg/h with a loading dose. The protein binding of cefpodoxime in rat plasma was determined using ultrafiltration. RESULTS: The average protein binding of cefpodoxime in rat plasma was 38%. The half-lives in plasma, muscle and lung were similar (approximately 5 h). After constant rate infusion, the free concentrations in the muscle and the lung were almost identical, but lower than total and free plasma concentrations. The data were modeled simultaneously using a two-compartmental body model. CONCLUSIONS: Free interstitial levels of cefpodoxime in muscle and lung tissue are very similar. Since muscle is more accessible than lung, free muscle concentrations may serve as a good surrogate for unbound concentrations in lung.

Animals↗

PubMedDate not supplied

Population pharmacokinetics of digoxin in Egyptian pediatric patients: impact of one data point utilization.

A population pharmacokinetic (PK) study was designed to estimate the PK parameters of digoxin among a selected group of Egyptian pediatric patients (n = 30) with mean age +/- SD and body weight +/- SD of 8.88 +/- 3.01 years and 23.9 +/- 5.8 kg, respectively. All patients had heart failure and were maintained on digoxin given orally. Nonlinear mixed effect modeling software version 5 (NONMEM Project Group, San Francisco, CA) and one-compartment modeling were used for fitting the data. A one-trough steady-state plasma concentration level of digoxin was used in the analysis. The population mean estimates for clearance (CL/f) and volume of distribution (V/f), in which f represents oral bioavailability, were 8.61 L/h and 450 L, respectively. Because of the limited number of samples per patient, regression analysis could not detect a correlation between patient covariates and estimated PK parameters. The analysis did not converge to obtain good parameter estimates. At least two samples per patient should be used to improve the PK estimation and allow better analysis of the relation between the potential covariates and estimated PK parameters.

Administration, Oral↗

PubMedDate not supplied

Application of two-point assay of digoxin serum concentration in studying population pharmacokinetics in Egyptian pediatric patients with heart failure: does it make sense?

Digoxin pharmacokinetics (PK) was studied among a selected group of Egyptian pediatric patients (n = 40) with an age range of 0.33 to 15 years. All the patients had heart failure and were maintained on i.v. digoxin (10 microg/kg/d in 2 equal doses). For population PK analysis, 2 serum samples of digoxin were taken per patient. From 30 patients' trough (before the next dose) and 4 hours postdose samples were obtained, while in the other 10 patients, 0.5- and 6-hour postdose samples were taken. Serum concentrations were measured by fluorescence polarization immunoassay. PK modeling was performed using NONMEM software on log-transformed serum digoxin data. The best structural covariate-free model was a linear 2-compartment model with an exponential error model for intersubject variability and an additive model for intrasubject variability. Serum creatinine (SCR) was a significant covariate for clearance. The final population PK parameters were CL (L/h) = 0.388 - [0.78 x (SCR-0.6)], V1 (L/kg) = 1.38, Q (L/h/kg) = 0.48, V2 (L/kg) = 9.11, where CL is the total body clearance, V1 and V2 are the apparent volumes of distribution in the central and peripheral compartments, and Q is intercompartment clearance. A bootstrap resampling for internal validation achieved excellent agreement with the original data sets for PK parameters. In conclusion, 2 points of digoxin concentration allow good regression analysis for clearance-covariate relationship. The inclusion of SCR into the final model might allow better selection of initial maintenance dose of the drug. A prospective study on larger sample size of pediatric patients is recommended for clinical validation of the final model.

Adolescent↗

PubMedDate not supplied

Isolation and HPLC quantitative analysis of antioxidant flavonoids from Alternanthera tenella Colla.

Phytochemical analysis of the antioxidant ethanolic extract of Alternanthera tenella Colla led to the isolation of six flavonoids, acacetin 8-C-[alpha-L-rhamnopyranosyl-(1 --> 2)-beta-D-glucopyranoside] (1), 2"-O-alpha-L-rhamnopyranosyl-vitexin (2), 2"-O-beta-D-glucopyranosyl-vitexin (3), vitexin (4), quercetin (5) and kaempferol (6). All the structures were established by ESI-MS and NMR spectroscopic methods. Antioxidant capacity of extract, fractions and isolated compounds was determined using the oxygen radical absorbance capacity (ORAC) assay and extract, fractions and flavonoids isolated showed antioxidant activity in vitro. Moreover, the total soluble phenolic contents of the extract and fractions were measured using the Folin-Ciocalteau reagent and the quantitative analysis of flavone C-glycosides major constituents was performed by HPLC.

Antioxidants↗

PubMedDate not supplied

What is the best marker for inhaled corticosteroid safety?

The development of modern corticosteroids has revolutionized the treatment and management of asthma. Importantly, to a great extent, it has reduced the incidence of systemic side effects. However, at high doses, inhaled corticosteroid therapy is not devoid of systemic side effects such as growth suppression, reduction in bone density, and cataracts. Hence, it becomes important to monitor these effects. The most commonly used parameters that are monitored for systemic steroid effects measure the endogenous cortisol secretion. Measured parameters allow a direct comparison of the degree of systemic activity, which is difficult, based on steroid drug levels, because of the difference in potency of the various compounds. Evaluation of endogenous cortisol concentrations is complicated because of the presence of a circadian rhythm with highest cortisol concentrations in the morning and trough concentrations around bedtime. However, methods are available that consider circadian cortisol secretion. Cortisol levels should be measured over 24 hours at steady state. The area between the serum cortisol concentrations in the control group and the suppressed group is recognized as a good cumulative marker of systemic steroid activity. Cortisol suppression is a more sensitive marker for inhaled corticosteroid safety than parameters that consider effects on bone or lymphocyte suppression. If an inhaled corticosteroid dosing regimen does not show any significant cortisol suppression based on 24-hour serum area under the curve values, it can be assumed that this treatment is safe and unlikely to present any clinically relevant safety with respect to systemic steroid activity.

Administration, Inhalation↗

PubMedDate not supplied

Corticosteroid pharmacokinetic/pharmacodynamic parameters and their relationship to safety and efficacy.

All inhaled corticosteroids (ICSs) exert their pharmacologic effects through the same mechanism. This review examines pharmacokinetic profiles of ICSs to explain the variations in efficacy and adverse effects seen with these agents and identify ideal properties for an optimal ICS. For optimum efficacy and safety, the ideal ICS would have high pulmonary bioavailability with pulmonary activation for targeted delivery, negligible oral bioavailability, high plasma protein binding, rapid systemic clearance, and sustained pulmonary residence to permit once-daily dosing.

Administration, Inhalation↗