Assessing project approval procedures as formalised forms of public participation.

Formalised public participation in project approval procedures is rarely addressed in technology assessment. Empirical data about public participation processes are taken into account even more rarely. This article explores the practice of public participation in infrastructure projects in the Federal Republic of Germany on the basis of empirical data from the period of 1990 to 2010.

Relative bioavailability and pharmacodynamic effects of methantheline compared with atropine in healthy subjects.

Objectives: Methantheline is a strong muscarinic receptor blocking drug used in the treatment of overactive bladder syndrome, hypersalivation and hyperhidrosis. To provide basic information on the pharmacokinetics, magnitude of pharmacodynamic (PD) effects and their correlations with plasma concentrations, we performed a clinical study in 12 healthy subjects receiving methantheline as immediate-release coated tablets (IR) or in watery solution (SOL) in comparison with atropine and placebo tablets.

Methods: The pharmacokinetics and influence of methantheline, atropine and placebo on salivation and accommodation and pupil function (pupillometry: diameter, response to light flash) were studied in a randomized, controlled study after the administration of 100 mg methantheline bromide as IR and in SOL (phase 1) and 1.

The talinolol double-peak phenomenon is likely caused by presystemic processing after uptake from gut lumen.

Purpose: Evaluation of the double-peak phenomenon during absorption of the beta(1)-selective blocker talinolol relative to paracetamol, which is well absorbed from all parts of the gut, and relative to vitamin A, which is absorbed via the lymphatic pathway.

Methods: Talinolol was given with paracetamol and retinyl palmitate in fast-disintegrating, enteric-coated, and rectal soft capsules to 8 fasting male healthy subjects (21-29 years, 68-86 kg). To evaluate whether the talinolol double-peak is associated with processes of food absorption, a breakfast was served 1 h after administration of a fast disintegrating capsule.

Carbamazepine regulates intestinal P-glycoprotein and multidrug resistance protein MRP2 and influences disposition of talinolol in humans.

Background And Methods: The antiepileptic drug carbamazepine is known to be an inducer of cytochrome P450 (CYP) 3A4 after binding to the nuclear pregnane X receptor. To evaluate whether it also regulates the multidrug transporter proteins P-glycoprotein (P-gp) and multidrug resistance protein MRP2 in humans, duodenal expression of multidrug resistance gene MDR1 messenger ribonucleic acid (mRNA) and MRP2 mRNA, content of P-gp and MRP2, and disposition of the nonmetabolized P-gp substrate talinolol after intravenous (30 mg) and long-term oral administration (100 mg for 19 days) were assessed in 7 healthy subjects (age, 23-35 years; body weight, 64-93 kg) before and after comedication of carbamazepine (600 mg for 14-18 days).

Results: Carbamazepine medication was associated with increased urinary excretion of D-glucaric acid and induction of carbamazepine elimination.

CYP2D6 genotype and induction of intestinal drug transporters by rifampin predict presystemic clearance of carvedilol in healthy subjects.

Background: Clinical trials have indicated that the combined beta- and alpha-adrenergic receptor blocker carvedilol improves the survival rate in patients with advanced chronic heart failure. The objective of our study was the identification and quantification of factors that modulate steady-state serum concentrations of carvedilol and its enantiomers and that may influence therapeutic efficacy and safety.

Methods: The influence of genetic variants of cytochrome P450 (CYP) 2D6 and CYP2C9 and of transporter proteins (P-glycoprotein, multidrug resistance protein 2 [MRP2]) on the disposition of carvedilol and its enantiomers after intravenous (5 mg) and long-term oral administration (25 mg for 7 days) was assessed in 12 healthy subjects.

Evaluation of the novel antiepileptic drug, AWD 131-138, for benzodiazepine-like discriminative stimulus and reinforcing effects in squirrel monkeys.

AWD 131-138 [1-(4-chlorophenyl)-4-morpholino-imidazolin-2-one], a new low-affinity partial benzodiazepine receptor agonist with potent anticonvulsant and anxiolytic properties in rodent models, was studied in squirrel monkeys trained to discriminate intramuscular (i.m.) injections of midazolam (0.

Variability of intestinal expression of P-glycoprotein in healthy volunteers as described by absorption of talinolol from four bioequivalent tablets.

The beta(1)-selective blocker talinolol is incompletely absorbed in man from an "absorption window" in the upper small intestine which is under control of P-glycoprotein. The following single dose, four-period, changeover study with 7 days washout in 36 healthy subjects (21 females, age 20-33 years) was designed to confirm bioequivalence of four marketed tablet formulations of talinolol with identical in vitro liberation and to deduce from the intrasubject and intersubject variability of talinolol pharmacokinetics on the variability of intestinal P-gp function. All point estimates of the primary criteria AUC(0-infinity) and C(max) for the comparison of the galenic forms were within 0.

Effect of levothyroxine administration on intestinal P-glycoprotein expression: consequences for drug disposition.

Objective: Thyroid function alters the pharmacokinetics of many drugs; one example is the cardiac glycoside digoxin. Because digoxin disposition is affected by intestinal expression of P-glycoprotein, we hypothesized that thyroid hormones may regulate P-glycoprotein and influence disposition of P-glycoprotein substrates.

Methods: Duodenal expression of P-glycoprotein measured by reverse transcriptase-polymerase chain reaction of MDR1 messenger ribonucleic acid (mRNA) and by immunohistochemical examination was studied in 8 healthy volunteers (4 men and 4 women; age range, 22-29 years; body weight, 59-89 kg) before and after coadministration with levothyroxine (200 microg orally for 17 days), which resulted in suppression of thyroid-stimulating hormone.

Circadian rhythm of serum cortisol after repeated inhalation of the new topical steroid ciclesonide.

Unlabelled: The new inhalative glucocorticoid ciclesonide which is activated in lung to a more potent metabolite was hypothesized to have low risk for systemic and local side-effects in man. Therefore, a placebo-controlled, randomized, double-blind, four-period, change-over equivalence study in 12 healthy male volunteers (age 21-28 yr, body weight 62-90 kg) was conducted to assess the influence of three dosage regimens (800 microg in the morning, 800 microg in the evening, 400 microg twice daily for 7 d, metered inhalers) on the circadian time serum cortisol rhythm.

Results: Serum cortisol showed the typical circadian rhythm.

Stereoselective disposition of talinolol in man.

The disposition of the beta-blocking drug talinolol is controlled by P-glycoprotein in man. Because talinolol is marketed as a racemate, we reevaluated the serum-concentration time profiles of talinolol of a previously published study with single intravenous (30 mg) and repeated oral talinolol (100 mg for 14 days) before and after comedication of rifampicin (600 mg per day for 9 days) in eight male healthy volunteers (age 22-26 years, body weight 67-84 kg) with respect to differences in the kinetic profiles of the two enantiomers S(-) talinolol and R(+) talinolol. Additionally, the metabolism of talinolol in human liver microsomes was examined.