Common structural requirements for heptahelical domain function in class A and class C G protein-coupled receptors.

G protein-coupled receptors (GPCRs) are key players in cell communication. Several classes of such receptors have been identified. Although all GPCRs possess a heptahelical domain directly activating G proteins, important structural and sequence differences within receptors from different classes suggested distinct activation mechanisms.

Pharmacokinetics and tolerability of formoterol in healthy volunteers after a single high dose of Foradil dry powder inhalation via Aerolizer.

Objective: The pharmacokinetics of the long-acting beta2-agonist formoterol fumarate, which is a racemate of the (S,S)- and (R,R)-enantiomers were evaluated in 12 healthy (eight male, four female) volunteers after a single inhaled high dose of 120 microg of formoterol fumarate. The tolerability and safety were also assessed.

Methods: Each volunteer inhaled the single 120-microg dose through the Aerolizer device within 2-5 min, using ten 12-microg dry powder capsules for inhalation.

Effect of food on the bioavailability of triclabendazole in patients with fascioliasis.

Aims: Preliminary results indicate higher absorption of triclabendazole (TCBZ) administered postprandially. Therefore, the influence of food on the pharmacokinetics of TCBZ and its active sulphoxide (TCBZ-SO) and sulphone (TCBZ-SO2) metabolites was investigated.

Methods: Two single doses (10 mg kg(-1)) of TCBZ were administered to 20 patients with fascioliasis.

The influence of food on the disposition of the antiepileptic rufinamide in healthy volunteers.

The effect of food on the pharmacokinetics of the antiepileptic rufinamide was investigated in healthy volunteers. Twelve subjects were treated with single pre-oral doses of 600 mg of rufinamide after overnight fasting or a fat and protein rich breakfast. Mean (+/- S.

Automated and sensitive method for the determination of formoterol in human plasma by high-performance liquid chromatography and electrochemical detection.

An automated high-performance liquid chromatography (HPLC) method for the determination of formoterol in human plasma with improved sensitivity has been developed and validated. Formoterol and CGP 47086, the internal standard, were extracted from plasma (1 ml) using a cation-exchange solid-phase extraction (SPE) cartridge. The compounds were eluted with pH 6 buffer solution-methanol (70:30, v/v) and the eluate was further diluted with water.

Bioequivalence assessment: a pharmaceutical industry perspective.

Various aspects of bioequivalence are investigated in this paper. Some aspects dealing with bioequivalence studies conducted either during the development of the drug or after its marketing will be presented and discussed: Bioequivalence of highly variable drugs with the associated problem of widening the acceptance range or alternative solutions. Bioequivalence for the final market image.

Automated analysis of a novel anti-epileptic compound, CGP 33,101, and its metabolite, CGP 47,292, in body fluids by high-performance liquid chromatography and liquid-solid extraction.

Automated procedures for the determination of CGP 33,101 in plasma and the simultaneous determination of CGP 33,101 and its carboxylic acid metabolite, CGP 47,292, in urine are described. Plasma was diluted with water and urine with a pH 2 buffer prior to extraction. The compounds were automatically extracted on reversed-phase extraction columns and injected onto an HPLC system by the automatic sample preparation with extraction columns (ASPEC) automate.

Automated microanalysis of oxcarbazepine and its monohydroxy and transdiol metabolites in plasma by liquid chromatography.

An automated high-performance liquid chromatographic method for the simultaneous determination of oxcarbazepine and its monohydroxy and transdiol metabolites in plasma is described. 5,6-Dihydro-11-oxo-11H-dibenz[b,e]azepine-5-carboxamide was used as internal standard. Liquid-solid extraction from plasma (100 microliters) on 50 mg Bond-Elut C18 cartridges was automatically performed by the Automatic Sample Preparation with Extraction Columns (ASPEC) system.

The effect of renal impairment on the pharmacokinetics of oxcarbazepine and its metabolites.

We have studied the effect of renal impairment on the pharmacokinetics of oxcarbazepine, its active monohydroxy-metabolite (which predominates in plasma), their glucuronides, and the inactive dihydroxy-metabolite after a single oral dose of oxcarbazepine (300 mg). Six subjects with normal renal function and 20 patients with various degrees of renal impairment participated. The mean areas under the plasma concentration-time curves of oxcarbazepine and its monohydroxy-metabolite were 2-2.

Pharmacokinetics of cadralazine and its hydrazino-metabolite in patients with renal impairment after repeated administration of 5 mg once daily.

Since the hydrazino-pyridazine metabolite of cadralazine, CGP 22 639 is believed to contribute to the activity of the drug, its pharmacokinetics and that of cadralazine were investigated in 8 hypertensive patients with renal impairment. The creatinine clearance (CLcr) of patients ranged from 10 to 60 ml/min. The concentrations of cadralazine in plasma and urine, and of CGP 22 639 (plus its possible hydrazones) in plasma were measured after single and repeated administration of 5 mg of cadralazine once daily.

Rapid determination of propyphenazone in plasma by high-performance liquid chromatography.

A rapid and simple high-performance liquid chromatographic assay for the determination of propyphenazone in plasma is described. Phenylbutazone was used as the internal standard. Plasma proteins were precipitated with acetonitrile before injection onto a 3-microns Supelcosil LC-18 column.

Automated microanalysis of carbamazepine and its epoxide and trans-diol metabolites in plasma by column liquid chromatography.

A fully automated high-performance liquid chromatographic procedure for the simultaneous determination of carbamazepine and its main metabolites, epoxycarbamazepine and dihydroxycarbamazepine, in plasma is described. Liquid-solid extraction on disposable C18 columns and reversed-phase chromatography on a 3 microns particle size C18 column were combined and automated by using the Automatic Sample Preparation with Extraction Columns system. Ultraviolet detection was performed at 210 nm.

Fast liquid chromatography for the determination of drugs in plasma and combination with liquid-solid extraction in a fully automated system.

Fast liquid chromatography was applied to the assay of several drugs in plasma. Short columns, 3.3-4 cm long, packed with C18 material, 3 microns particle size, were used.

[Distomatosis of the bile ducts. Value of retrograde cholangiography. Efficacy of triclabendazole].

A case of chronic biliary fascioliasis is reported, which was confirmed by endoscopic retrograde cholangiography. After unsuccessful attempts of treatment with classic antiparasitic drugs, cure was obtained with triclabendazole the absorption of which was studied.

Concentrations of amocarzine in plasma of 71 Ecuadorian patients of two different races receiving 3 mg/kg b.i.d. and 5 mg/kg o.d. oral postprandial doses for 3 days.

The possible influence of sex, race and of postprandial administration conditions (either immediately after the end of meal or one hour later) on the plasma concentrations of amocarzine and its N-oxide metabolite, CGP 13 231, was investigated. 71 Ecuadorian patients (48 males and 23 females) of two different races (Indio and Negro) infected with Onchocerca volvulus participated in the study. The concentrations were measured on day 3 at times 3 and 6 h after postprandial administration in the morning of a treatment with either a dose of 5 mg/kg of amocarzine once daily (12 patients) or 3 mg/kg twice daily (59 patients) for 3 days.

Influence of food related to dose on the pharmacokinetics of amocarzine and of its N-oxide metabolite, CGP 13 231, after oral administration to 20 onchocerciasis male patients from Guatemala.

Twenty male patients from Guatemala infected with Onchocerca volvulus received a 3 mg/kg oral dose of amocarzine twice daily for three days. The patients were randomly assigned to the sequence fasting/non-fasting and non-fasting/fasting for the morning administration on days 1 and 3. All other doses were given after food intake.

Onchocercacidal effect of three drug regimens of amocarzine in 148 patients of two races and both sexes from Esmeraldas, Ecuador.

The objective of this multidisciplinary clinical investigation was to test whether amocarzine was absorbed effectively and safely in patients of two races and either sex infected with Onchocerca volvulus while living in the holoendemic area of Esmeraldas Province, Ecuador. The prerequisite for a systemic onchocercacidal effect is the regular absorption of orally administered amocarzine. Single dosing after overnight fasting proved to produce irregular absorption of amocarzine, although some microfilaricidal effect was achieved.

Amocarzine investigated as oral onchocercacidal drug in 272 adult male patients from Guatemala. Results from three dose regimens spread over three days.

The clinical investigations with three types of a three days regimen of amocarzine permitted to adjust the fixed dosing to the body weight related dosing and subsequently the administration of amocarzine from fasting state to drug intake after food. The main objective to reach a dose with predictable and sustained absorption was achieved, and this in turn proved to be onchocercacidal and safe. A combined clinicopharmacokinetic study showed enhancement and consistency of amocarzine absorption after food.

Pharmacokinetics of cadralazine in a large group of hypertensive patients chronically treated with cadralazine: advantage over a conventional study in a small group of patients.

The concentrations of cadralazine in plasma were studied in 101 hypertensive patients treated with oral doses of 10, 15, or 20 mg of cadralazine once daily. Most of the patients received additionally a beta-blocking drug (n = 87) and a diuretic (n = 52). Few blood samples were collected in each patient on several occasions during the treatment, which usually lasted for more than 6 months.

The influence of food on the pharmacokinetics of CGP 6140 (amocarzine) after oral administration of a 1200 mg single dose to patients with onchocerciasis.

Eleven male patients from Mali with Onchocerca volvulus infections received in random order a 1200 mg single oral dose of CGP 6140 after an overnight fast and after food intake. The concentrations of CGP 6140 and of its N-oxide metabolite, CGP 13231, were measured in plasma and urine. Mean (+/- s.

Pharmacokinetics of CGP 6140 (amocarzine) after oral administration of single 100-1600 mg doses to patients with onchocerciasis.

The concentrations of CGP 6140 [4-nitro-4'-(N-methyl-piperazinylthiocarbonylamido)-diphenylamine] and of its N-oxide metabolite, CGP 13,231, were measured in plasma and urine after single oral dose of 100-1600 mg of CGP 6140 to 41 fasted Ghanaian patients with Onchocerca volvulus infections. The absorption of CGP 6140 was rapid and its terminal elimination half-life was about 3 h. The plasma concentrations of CGP 6140 were essentially proportional to the dose.