Irbesartan does not affect the steady-state pharmacodynamics and pharmacokinetics of warfarin.

Objectives: To determine whether the initiation or titration of irbesartan alters the pharmacodynamics and/or pharmacokinetics of warfarin in a clinically significant manner, thereby requiring additional monitoring of the anticoagulant effect of warfarin.

Methods: Daily doses of warfarin were administered to 16 healthy males for 21 days (10 mg on day 1 and 2.5-10 mg on days 2-21).

Influence of food intake on the bioavailability of urapidil in healthy volunteers.

The influence of food intake on the pharmacokinetics of a single dose (30 mg) of urapidil in a tablet and a sustained-release capsule form were examined in 12 healthy volunteers in a double crossover trial. Drug administration under fasting conditions requires that a standardized breakfast be eaten, 4 h after drug intake. Drug application with breakfast requires drug intake with the standardized breakfast.

[The pharmacokinetics and bioavailability of urapidil. In vitro/in vivo correlations of different experimental formulations].

The pharmacokinetic parameters, including the relative bioavailabilities of two experimental batches of a 60-mg urapidil slow release-capsule and a 30-mg urapidil drinking ampoule (Ebrantil) had to be evaluated in a randomized, three-period change-over study with 12 healthy volunteers after single dosing. The appropriate parameters for the capsule formulations were compared with their dissolution rates obtained by different in vitro models. The capsules showed different half-change, but comparable single-fluid dissolution profiles.

Pharmacokinetic profile of metaclazepam (Talis), a new 1.4-benzodiazepine. Influence of different dosage regimens on the pharmacokinetic profile of metaclazepam and its main metabolite under steady-state conditions.

The pharmacokinetic parameters of the new 1.4-benzodiazepine metaclazepam (Talis) were investigated. In particular, the question of whether the drug and/or its main metabolite accumulates in the body under steady-state conditions was studied.

[Pharmacokinetics and bioavailability of diphenhydramine in man].

By the presented study the relative bioavailabilities and some important pharmacokinetic parameters should be evaluated after oral application of a single-dose of three different diphenhydramine (DPH, 2-diphenylmethoxy-N,N-dimethylethylamine)preparations in a randomized, cross-over design to 12 healthy volunteers. Additionally, some simple pharmacodynamic measurements of the volunteer's vigilance were performed and the question whether a combination with 8-chlorotheophylline influences the pharmacokinetic and/or pharmacodynamic profile of DPH was investigated. As the test preparations (Benocten as a tablet = A, as a buffered solution = B) contained 50 mg of DPH-HCl, but the reference preparation (= C) only 31 mg of DPH-HCl (+ 23 mg 8-chlorotheophylline), the biometric-statistic calculations had to be done with and without dose correction.

Comparison of the pharmacokinetic profile of metaclazepam in old and young volunteers.

A single-centre, open, Phase I-study comparison of the pharmacokinetics of a single dose of metaclazepam 10 mg, a new 1,4-benzodiazepine has been done in 10 older and 20 younger volunteers. No important age-related effect was found on the kinetics of metaclazepam or its N-desmethyl derivative, the principal metabolite in man.

[Comparative studies on the tolerance of bioequivalent doses of intravenous methylxanthine preparations in healthy subjects].

In a comparative tolerance study with two different intravenous methylxanthine preparations, a theophylline-ethylendiamine preparation (TE-reference preparation) was tested against a combination of theophylline, proxyphylline (7-(2-hydroxypropyl)-theophylline) and diprophylline (7-(2,3-dihydroxypropyl)-theophylline) (Neobiphyllin; TPD = test preparation) in 10 healthy volunteers by a single blind cross-over design. Both preparations were infused under continuous control of vital parameters (blood pressure, pulse, respiration frequency, heart rhythm) as infusions (1 ampoule with 800 mg TPD or 1 short-infusion with 480 mg of TE for 20 min, each) up to the individual tolerance limit or the pre-defined limit of 3 ampoules/short infusions, respectively. The maximum tolerated infusion time and the serum levels at which the first side-effects appeared, were compared.

[The bioavailability and pharmacokinetics of two carbocysteine preparations after single and multiple dosing].

The relative bioavailabilities and pharmacokinetic profiles of 2 carbocisteine preparations (capsules, granulate) were evaluated in a single dose and a steady state study. 10 healthy volunteers took in a randomized, 2fold cross over design 750 mg 3-(carboxymethylthio)alanine (carbocisteine, Transbronchin) (1 portion of the granulate or 2 capsules) as a single dose or for 4 days 3 times a day (every 8 h) 1 portion of the granulate or 2 capsules, respectively. During the saturation phase the pre-dose serum levels in the morning were determined and on day 5 - after a last dosing the elimination kinetics were evaluated.

[Comparative study of the bioavailability and pharmacokinetics of isosorbide dinitrate formulations in retard form and in standard preparations by determination of isosorbide-5-mononitrate].

The aim of the study was to determine the relative bioavailability and the pharmacokinetic parameters following administration of a slow-release formulation of isosorbide dinitrate (ISDN, Isdin) capsules (20, 40 and 60 mg). A gas chromatographic method was used to determine the plasma concentrations of ISDN and isosorbide-5-mononitrate (IS-5-MN). All of the required pharmacokinetic parameters were ascertained.

Quantitative determination of bencyclane in human plasma by capillary gas chromatography/chemical ionization mass spectrometry.

Since 10 years there is a phenomenal increase in the use of mass spectrometry, combined with (capillary-) gas chromatography and dedicated data systems for the rapid, reliable, sensitive and selective determination of xenobiotics (drugs, their degradation/biotransformation products etc.) in biological fluids. This applies especially since the introduction of newer developments in ionization techniques (CI, DCI, FAB) and gas chromatographic column technology (fused silica, bonded phase columns).

Quantitative determination of diphenhydramine and orphenadrine in human serum by capillary gas chromatography.

Diphenhydramine has been in medical use for 35 years as an antihistamine and hypnotic. We evaluated the pharmacokinetic parameters, which are not only important for disposition studies, in the serum of 10 volunteers who received a single dose of 31 mg diphenhydramine. For this purpose a suitable capillary GC-method was developed, which has a detection limit of 2 micrograms/l (serum); the calibration curve is linear between 2.

[Mass spectrometric data on some drugs, their biotransformation products and intermediate products of illegal synthesized narcotics].

Additional mass spectral data of some rather unusual drugs and their biotransformation-products are presented updating the three large and authoritative mass spectra data collections for forensic/clinical toxicological purposes published by Finkle, Foltz and Saferstein et al. Furthermore mass-spectra data of chemicals, intermediates, by-products and final products of illegal drug syntheses are summarized in one chapter.

[Comparative test of the bioavailability and pharmacokinetics of 2 oxazepam preparations using high-pressure liquid chromatography].

The relative bioavailability and pharmacokinetic profile of two oxazepam preparations were evaluated in 12 normal volunteers by a newly developed HPLC-method. After oral application of one tablet of the test (Noctazepam) and reference preparation, respectively, no statistically significant differences of the AUC, Cmax Tmax and t1/2 were found. As compared to the reference preparation the relative bioavailability of the test preparation as 110%; both preparations are therefore bioequivalent.

[Gas chromatographic/mass spectrometric determinations of indomethacin serum levels in the course of pharmacokinetic studies in healthy volunteers].

For 4 different brands of indomethacin preparations the in vitro dissolution data as well as their relative bioavailabilities were determined. The in vitro tests were performed by the rotating basket method; the quantitative determinations of the serum-levels were determined by an gas chromatographic/mass spectrometric assay employing registration of the characteristic selected ion current profiles of the compound. Furthermore a special method for synthesis of the needed internal standard was also developed.

[Comparative studies on the in vitro dissolution and bioavailability of various acetylsalicylic acid preparations].

For five different brands of acetylsalicylic acid (ASA) preparations the in vitro/in vivo data were determined and tested for comparability. The in vitro dissolution rates were determined by two different methods (Paddle, rotating basket) whereas the in vivo data were obtained from 15 volunteers in a 5-fold cross-over trial. The markedly worse in vitro dissolution (rotating basket) of one preparation is in contrast to the in vivo data which showed bioequivalency of all five preparations.

[Analysis and renal excretion of pirisudanol (Stivane)].

The chromatographic and spectroscopic properties (TLC; UV; IR; 1H-NMR; GC/MS) of the psychostimulant Stivane (dimaleate;I) are presented in detail, describing some analytic peculiarities of the pure substance as well. Moreover, the results of the renal excretion studies are reported: after hydrolysis in each of the acidic and basic urine extracts a degradation product--but no unchanged drug--could be detected.

[Bioavailability of glycerol trinitrate (nitroglycerin) from an ointment preparation].

After application of an ointment of glycerol trinitrate (nitroglycerin, Nitrofortin; in the following briefly called GTN) the bioavailability of the unchanged GTN was evaluated. For that purpose a gas chromatographic/mass spectrometric method was employed, the only method which guarantees the selectivity and sensitivity necessary for this kind of studies. In this respect selectivity means that only the unchanged drug is determined and degradation and/or biotransformation products are measured only if needed.

Determination of the psychostimulants pemoline, fenozolone and thozalinone in human urine by gas chromatography/mass spectrometry and thin layer chromatography.

Detection of the psychostimulants pemoline (Tradon), fenozolone (Ordinator) and thozalinone (Stimsen) in biological samples (urine) presents certain experimental difficulties. These substances were therefore converted by acid hydrolysis to their common hydrolysis product 5-phenyl-2,4-oxazolidinedione, which can be detected with high sensitivity and selectivity by thin layer chromatography. After silylation with N-methyl-N-trimethylsilyltrifluoroacetamide/trimethylchlorosilane quantitative results can be obtained from the same extract by the proposed GC/MS-method.

[FAB (fast atom bombardment)-mass spectrometry. A new study method in the hands of the (forensic) toxicologist].

The FAB (Fast Atom Bombardment)-mass spectrometric ionization technique, which has now been available for about 1 year, has been successfully employed in forensic toxicology. The mass spectral behaviour of some representative drug-glucuronides (Codeine, p-Nitrophenol and 2-Phenyl-1-propanol) were studied by positive- and negative-ion-FAB-MS. The presented promising results may be of some interest, not only for the analytical toxicologist.

[Detection of pentazocin (Fortral) in human urine: gas chromatographic/mass spectrometric studies].

After oral application of pentacozine (Fortral) besides the unchanged drug some further excretion products were detected by glc/ms in human urine. For their identification e.i.

[Biotransformation of doxylamine: isolation, identification and synthesis of some metabolites (author's transl)].

After administration of therapeutic doses of doxylamine, the unchanged drug(I) and five degradation products were detected in human urine; their chemical structures are discussed and - to some extent - confirmed by synthesis. The results show that biotransformation of doxylamine in man takes place by the following routes: successive dealkylations at the nitrogen atom, giving N-demethyl-doxylamine(II) and N.N-didemethyl-doxylamine(II); cleavage at the benzhydrylether-function, resulting in the formation of 1-phenyl-1-(2-pyridyl)-ethanol(V), 1-phenyl-1-(2-pyridyl)-ethane(VI) and 1-phenyl-1-(2-pyridyl)-ethene(VII).

[Quantitative determination of mefexamide and its main degradation product desmethyl-mefexamide in human urine after ingestion of therapeutic doses (author's transl)].

After oral ingestion of 400 mg Mefexamidehydrochloride for Mefexamide (I) and its main degradation product Desmethyl-Mefexamide (II) the following pharmakokinetic parameters have been determined: 1. Elimination of I and II follows 1st order kinetics. 2.