Comparison of talinolol and atenolol effects on blood pressure in relation to lipid and glucose metabolic parameters. Results from the TALIP study.

Aims: The primary objective of this double-blind, randomized, parallel-group study was to compare the influence ofthe selective beta1-receptor antagonists talinolol (100 mg) and atenolol (50 mg) on the lipid metabolism in hyperlipemic patients with mild to moderate hypertension after 12 weeks of treatment. As a secondary endpoint, the influence of the drug on blood pressure, pulse rate as well as glucose metabolism were examined. Furthermore, pharmacokinetic parameters were assessed.

Microdialysis of triamcinolone acetonide in rat muscle.

The objective of this study was to compare plasma and muscle concentrations of triamcinolone acetonide (TA) in the rat by microdialysis. Microdialysis experiments were carried out at steady state in rats after an initial I.V.

Single- and multiple-dose pharmacokinetics of oral creatine.

Supplementation with exogenous creatine (Cr) has shown physiological benefits in humans, but little is known about the pharmacokinetics of Cr in humans. Six healthy males completed an open-label study consisting of a full pharmacokinetic analysis following a single oral dose of Cr monohydrate (71 mg kg-1) and at steady-state after 6 days of Cr administration (71 mg kg-1 qid). After the single oral dose, the clearance (CL/F) was 0.

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.

Pharmacokinetics and bioavailability of herbal medicinal products.

The use of herbs for treating various ailments dates back several centuries. Usually, herbal medicine has relied on tradition that may or may not be supported by empirical data. The belief that natural medicines are much safer than synthetic drugs has gained popularity in recent years and led to tremendous growth of phytopharmaceutical usage.

Novel formulations of cetrorelix acetate in healthy men: pharmacodynamic effects and noncompartmental pharmacokinetics.

The objective of this study was to investigate the effects on the pharmacodynamics and noncompartmental pharmacokinetics after weekly subcutaneous administration of novel formulations of cetrorelix acetate in healthy men. In a randomized parallel-group study, single subcutaneous doses of cetrorelix acetate (concentration: 2.5 mg peptide base/ml) dissolved in aqueous gluconic acid (CET/glu, dose: 5 or 10 mg peptide base) or in water (CET/wat, dose: 10 mg peptide base) were given to 36 subjects once weekly in the morning for 4 weeks.

Systemic availability and pharmacokinetics of thymol in humans.

Essential oil compounds such as found in thyme extract are established for the therapy of chronic and acute bronchitis. Various pharmacodynamic activities for thyme extract and the essential thyme oil, respectively, have been demonstrated in vitro, but availability of these compounds in the respective target organs has not been proven. Thus, investigation of absorption, distribution, metabolism, and excretion are necessary to provide the link between in vitro effects and in vivo studies.

Interstitial tissue concentrations of cefpodoxime.

Microdialysis is a technique that allows the measurement of concentrations of free antibiotic in tissue. The free antibiotic concentration is responsible for the antibacterial effect at the target site. We used microdialysis in animal and human studies to investigate the tissue penetration of cefpodoxime.

How important are gender differences in pharmacokinetics?

Gender-related differences in pharmacokinetics have frequently been considered as potentially important determinants for the clinical effectiveness of drug therapy. The mechanistic processes underlying gender-specific pharmacokinetics can be divided into molecular and physiological factors. Major molecular factors involved in drug disposition include drug transporters and drug-metabolising enzymes.

Standardization of pharmacokinetic/pharmacodynamic (PK/PD) terminology for anti-infective drugs.

Over the last decades, the interest in the relationships between the pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobial agents has increased and, therefore, the use of PK/PD indices and expressions has spread widely. The appropriate definition and use of these parameters is a matter of controversy. This paper contains a proposal to use PK/PD expressions for antimicrobial agents and their units in a uniform manner.

Rational dosing of antibiotics: the use of plasma concentrations versus tissue concentrations.

At the moment, the most common pharmacokinetic/pharmacodynamic (PK/PD) approaches for anti-infective agents, such as time above MIC, C(max)/MIC and AUC(24)/MIC, rely on plasma concentration as the PK input value and minimum inhibitory concentration (MIC) as the PD input value. However, only the free tissue concentrations of antibiotics at the target site are responsible for the therapeutic effect. Using plasma concentrations frequently overestimates the target site concentrations and therefore clinical efficacy.

Comparative target site pharmacokinetics of immediate- and modified-release formulations of cefaclor in humans.

Optimal dosing of beta-lactam antibiotics aims at maximizing the time at which drug levels in the interstitial space fluid (ISF)--the fluid that surrounds the causative microorganisms at the target site--exceed the minimal inhibitory concentration (MIC). One potentially attractive strategy to achieve this goal is to administer antibiotics as oral sustained-release formulations. The present study was designed to test the hypothesis that sustained-release formulations could lead to a more suitable pharmacokinetic profile in the ISF at the relevant target site.

Bioavailability and metabolism of mometasone furoate: pharmacology versus methodology.

The degree of systemic exposure ofter inhalation of corticosteroids is of great clinical concern. For optimum outcome, the pulmonary deposition should be sufficiently high to produce the desired anti-inflammatory effect in the lungs, whereas the plasma concentrations due to the absorption of the corticosteroid from the lung and the gut should be minimal. Recently, it has been reported that inhaled mometasone furoate has a systemic bioavailability of less than 1%, which is much lower than other corticosteroids currently available.

Soft cannabinoid analogues as potential anti-glaucoma agents.

Cannabinoids are able to reduce elevated intraocular pressure; however, their use in glaucoma treatment is not approved due to severe systemic side effects. New cannabinoid derivatives have been designed based on a retrometabolic/soft drug approach; they were expected to have local effect, but not systemic side effects. Lead compounds and soft analogues were prepared using Pechmann condensation.

Pharmacokinetic/pharmacodynamic studies in drug product development.

In the quest of ways for rationalizing and accelerating drug product development, integrated pharmacokinetic/pharmacodynamic (PK/PD) concepts provide a highly promising tool. PK/PD modeling concepts can be applied in all stages of preclinical and clinical drug development, and their benefits are multifold. At the preclinical stage, potential applications might comprise the evaluation of in vivo potency and intrinsic activity, the identification of bio-/surrogate markers, as well as dosage form and regimen selection and optimization.

Single-dose and steady-state pharmacokinetic and pharmacodynamic evaluation of therapeutically clinically equivalent doses of inhaled fluticasone propionate and budesonide, given as Diskus or Turbohaler dry-powder inhalers to healthy subjects.

Direct comparisons of the pharmacokinetic (PK) and systemic pharmacodynamic (PD) properties of inhaled corticosteroids after single and multiple dosing in the same subjects are scarce. The objective of this study was to compare thePK/PDproperties of clinically equivalent, single, and multiple doses of dry-powder formulations of inhaled fluticasone propionate (FP 200 and 500 microg via Diskus) and budesonide (BUD, 400 and 1,000 microg via Turbohaler). Fourteen healthy subjects completed a double-blind, double-dummy, randomized, placebo-controlled, five-way crossover study consisting of a single dose administered at 8 a.

An interactive algorithm for the assessment of cumulative cortisol suppression during inhaled corticosteroid therapy.

The objective of the study was to develop an algorithm based on a pharmacokinetic-pharmacodynamic (PK/PD) modeling approach to quantify and predict cumulative cortisol suppression (CCS) as a surrogate marker for the systemic activity of inhaled corticosteroid therapy. Two Excel spreadsheets, one for single dose and another for steady-state multiple doses of inhaled steroids, were developed for predicting CCS. Four of the commonly used inhaled steroids were chosen for the purposes of simulation: fluticasone propionate (FP), budesonide (BUD), flunisolide (FLU), and triamcinolone acetonide (TAA).

Penetration of cefaclor into the interstitial space fluid of skeletal muscle and lung tissue in rats.

Purpose: To measure and compare the penetration of cefaclor from the plasma compartment into the interstitial space of lung and skeletal muscle in rats and to integrate the data in a pharmacokinetic model.

Methods: Unbound interstitial concentrations in muscle and lung were measured by in vivo microdialysis following i.v.

Current concepts in pharmacokinetics and their implications for clinical medicine.

The history of medicine provides ample evidence of the physicians' struggle with the subject of appropriate drug dosing. Recent studies indicate that drug-related mortality due to inadequate dosing principles still is a leading cause of death, only surpassed by cardiovascular diseases, cancer and stroke. In an effort to rationalize drug therapy, pharmacokinetic (PK) principles were introduced in medical practice in the early 1970s, mainly in the field of therapeutic drug monitoring (TDM).

Microdialysis. A novel tool for clinical studies of anti-infective agents.

In vivo microdialysis (MD) is an innovative clinical technique that has been employed in preclinical research and metabolic studies in patients for more than a decade. Recently, MD has been adopted for human drug studies and has opened up the opportunity to quantify tissue drug distribution in vivo. The particular advantage of MD for the anti-infective field relates to the fact that MD allows for online measurement of the unbound, pharmacologically active drug fraction in the interstitial space fluid (ISF), the anatomically defined target site for most bacterial infections.

Evaluation of pulmonary absorption using pharmacokinetic methods.

When assessing inhaled drug absorption, standard pharmacokinetic analyses cannot differentiate drug that reaches the systemic circulation from the lungs from that of the gut. Pulmonary absorption kinetics can be assessed for drugs with negligible gastrointestinal absorption or for drugs that are eliminated via first-pass metabolism. For other drugs, pulmonary absorption kinetics can be studied by blocking gastrointestinal absorption with charcoal, or by studying absorption during the first 30 minutes post inhalation before appreciable oral absorption has occurred.

Pharmacokinetics and rectal bioavailability of hydrocortisone acetate after single and multiple administration in healthy subjects and patients.

The pharmacokinetics and bioavailability of hydrocortisone after rectal administration of a hydrocortisone acetate foam were determined after single and multiple dosing in healthy subjects as well as in patients with inflammatory bowel disease. Endogenous hydrocortisone was suppressed by dexamethasone administration. Plasma levels were compared with those observed after intravenous administration of hydrocortisone.

Pharmacokinetics and bioavailability of quercetin glycosides in humans.

Due to its potentially beneficial impact on human health, the polyphenol quercetin has come into the focus of medicinal interest. However, data on the bioavailability of quercetin after oral intake are scarce and contradictory. Previous investigations indicate that the disposition of quercetin may depend on the sugar moiety of the glycoside or the plant matrix.

Population pharmacokinetics of intramuscular quinine in children with severe malaria.

We present the first population pharmacokinetic analysis of quinine in patients with Plasmodium falciparum malaria. Ghanaian children (n = 120; aged 12 months to 10 years) with severe malaria received an intramuscular loading dose of quinine dihydrochloride (20 mg/kg of body weight). A two-compartment model with first-order absorption and elimination gave post hoc estimates for pharmacokinetic parameters that were consistent with those derived from non-population pharmacokinetic studies (clearance [CL] = 0.