Search PubMed⌕ Search

Biomedical subjects

R Oertel

Publications and source records attributed to R Oertel.

At least 37 records · Page 2Linked to original sources
PubMed1999

Sensitive method for the determination of the antiarrhythmic drug detajmium in serum by solid-phase extraction and high-performance liquid chromatography with fluorimetric detection.

The objective of this study was to develop a very sensitive and selective method for the determination of detajmium (4-3-diethylamino-2-hydroxypropyl-ajmaline), a sodium-channel-blocking drug with antiarrhythmic properties, in serum. A high-performance liquid chromatography (HPLC) method with solid-phase extraction and fluorimetric detection has been applied. Serum samples were diluted with phosphate buffer (pH 3.5) and the extraction of detajmium and ajmaline, which was used as an internal standard, was carried out with Oasis cartridges (Waters). The chromatographic separation was performed on a RP18 column. The limit of quantification for serum samples of detajmium was 1 ng/ml with good reproducibility (R.S.D. < 15%) and a linear response from 1 to 200 ng/ml. The described method is highly sensitive and specific for the determination of detajmium in serum of patients and volunteers.

Ajmaline↗
PubMed1999

Solid-phase extraction and high-performance liquid chromatographic determination of articainic and its metabolite articainic acid in human serum.

A new method is described using solid-phase extraction (SPE) for preconcentration of articaine and the metabolite articainic acid and high-performance liquid chromatography (HPLC) for the determination of both compounds in human serum. Articaine and articainic acid were extracted in one step with SDB-RPS disk cartridges after precipitation of the serum proteins by perchloric acid. The HPLC separation was then performed on a reversed-phase C8 column using phosphate buffer-acetonitrile (88:12, v/v). UV absorption at 274 nm was used for measuring the analytes with a low limit of quantitation of about 10 ng/ml, which is appropriate for pharmacokinetic studies of low dose submucosal injections of the local anaesthetic agent articaine hydrochloride in dentistry.

Anesthetics, Local↗
PubMed1999

Intestinal secretion of intravenous talinolol is inhibited by luminal R-verapamil.

OBJECTIVE: To examine the secretion of the beta1-adrenergic receptor antagonist talinolol into the small intestine during its intravenous administration and to show the relevance of the P-glycoprotein-modulating drug verapamil for this secretory transport mechanism in humans. METHODS: In six healthy volunteers the intestinal steady-state perfusion technique (triple lumen tubing system) was used for measuring the appearance of talinolol within the small intestine while the drug was infused intravenously. During four of the seven perfusions performed, the perfusion fluid was changed from a verapamil-free solution and talinolol appearance was measured while a R-verapamil-containing solution (565 micromol/L) was perfused. RESULTS: Talinolol was transported into the intestinal lumen up to a concentration gradient between lumen and blood of about 5.5:1. While perfusing the small intestine with a verapamil-free solution, the intestinal secretion rate of talinolol ranged from 1.94 to 6.62 microg/min per 30 cm length of the intestine (median values). Perfusion of a R-verapamil-containing perfusion fluid resulted in lower secretion rates (0.59 to 3.71 microg/30 cm x min), corresponding to 29% to 56% of the values obtained without verapamil supplied intraluminally. CONCLUSION: Intravenously administered talinolol is actively secreted into the human small intestine. This secretion is reduced by the intraluminal supply of the P-glycoprotein modulating drug R-verapamil. This gives further rationale for P-glycoprotein-mediated intestinal drug secretion as a cause for incomplete oral bioavailability and for drug interactions during intestinal absorption.

Adrenergic beta-Antagonists↗
PubMed1999

Unexpected effect of verapamil on oral bioavailability of the beta-blocker talinolol in humans.

PURPOSE: To quantitate the effect of verapamil administered orally, a calcium channel blocker and potent inhibitor of P-glycoprotein on oral pharmacokinetics of the beta1-adrenergic receptor antagonist talinolol, a substrate of P-glycoprotein. SUBJECTS AND METHODS: In a randomized, crossover placebo-controlled study, oral pharmacokinetics of talinolol (50 mg) after concomitant administration of single doses of R-verapamil (120 mg) or placebo were investigated in 9 healthy volunteers. Concentrations of talinolol, verapamil, and its main metabolite norverapamil were measured in serum with HPLC. Concentrations of talinolol were also measured in urine by HPLC. Standard pharmacokinetic parameters were calculated with noncompartmental procedures. RESULTS: The area under the concentration-time curve for talinolol from 0 to 24 hours was significantly decreased after R-verapamil versus placebo (721+/-231 ng x h x mL(-1) versus 945+/-188 ng x h x mL(-1); P < .01). Maximum serum concentration of talinolol was reached significantly earlier after R-verapamil compared with placebo (P < .05). Coadministration of R-verapamil did not affect the renal clearance or half-life of talinolol. Serum pharmacokinetics are paralleled by the results derived from urine concentrations of talinolol. CONCLUSION: This is the first study to show a decreased oral bioavailability of a P-glycoprotein substrate (talinolol) in humans as a result of coadministration of verapamil. This effect is assumed to be caused by changes of the intestinal net absorption of talinolol because its renal clearance remains unaffected by administration of R-verapamil. This unexpected effect of R-verapamil is most likely dose dependent as a result of an interplay between intestinal P-glycoprotein and gut metabolism.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Determination of drugs in biological fluids by high-performance liquid chromatography with on-line sample processing.

An automated two column HPLC system with the new packing material LiChrospher RP-18 ADS (alkyl-diol-silica) was tested for the determination of several drugs and metabolites (talinolol, celiprolol, metoprolol, oxprenolol, triamterene, trimethoprim, tiracizine, articaine, detajmium, ajmaline, lamotrigine) in various biological fluids (serum, urine, intestinal aspirates, supernatants of cell cultures and supernatants after protein denaturation). The method allows the direct injection of biological fluids into a reversed-phase HPLC system and on-line clean-up and sample enrichment by a column-switching technique. Precision, accuracy and sensitivity were similar to conventional assays as described in the literature. With this new method it was possible to measure drug concentrations in various biological fluids without changing the sample preparation procedure. In some cases an additional sample preparation like protein denaturation or solid-phase extraction was advantageous to enhance the sensitivity of the method and the life-time of the ADS column.

Autoanalysis↗
PubMed1998

Pharmacokinetics and pharmacodynamics of scopolamine after subcutaneous administration.

The effects of subcutaneously administered scopolamine on quantitative electroencephalogram (qEEG) and cognitive performance were evaluated and correlated with pharmacokinetic parameters in a randomized, double-blind placebo-controlled crossover study of 10 healthy male volunteers. Changes in qEEG and cognition were determined for 8 hours after drug administration. Scopolamine produced dose- and time-dependent impairments of attention and memory and a time-dependent increase in delta power (1.25-4.50 Hz) and a decrease in fast alpha power (9.75-12.50 Hz) on qEEG compared with placebo. Maximum serum concentrations of scopolamine occurred 10 to 30 minutes after drug administration. Mean peak serum concentrations (free base) were 3.27, 8.99, and 18.81 ng/mL after administration of 0.4, 0.6 mg, and 0.8 mg scopolamine, respectively. Elimination half-life was approximately 220 minutes. The findings indicate temporary changes in qEEG and psychometric tests, and support the possible use of such a testing model for impaired cognitive functions such as age-related memory disturbances.

Adult↗
PubMed1997

"Reduction" of CGG trinucleotide expansion from mother to offspring in seven fragile-X families.

Apparent reduction in the size of the CGG repeat is reported from seven fragile-X mothers to nine offspring in seven extended families. The overall frequency of the reduction amongst 121 fragile-X mother-fragile-X child transmissions was 7.4%, compared with an 18% reduction in fragile-X father-fragile-X daughter transmissions, but ascertainment bias may account for some underestimation of the frequency of reductions, especially between mothers and their offspring. In one mother-son transmission, a premutation present in the son (with a full mutation present in the mother) was unmethylated. This may be the result of either demethylation with reduction, or undetected mosaicism in the mother. There was no obvious increase in the level of intellectual performance in female offspring who received a reduced fragment from their mothers. Several mechanisms leading to apparent reduction, such as germline mosaicism, deletion or replication slippage, should be considered.

Adolescent↗
PubMed1997

Clinical pharmacokinetics of articaine.

Articaine is the most widely used local anaesthetic agent in dentistry in a number of European countries. The amide structure of articaine is similar to that of other local anaesthetics, but it contains an additional ester group which is quickly hydrolysed by esterases. High performance liquid chromatography has been used to determine the concentrations of articaine and its metabolite articainic acid in serum. Rapid sample preparation is critical in the accurate determination of articaine serum concentrations, since blood and serum are the sites of metabolism. The time to maximum drug concentrations of articaine occurs about 10 to 15 minutes after submucosal injection of articaine 4% 80 mg, irrespective of epinephrine (adrenaline). The mean maximum plasma drug concentration is about 400 micrograms/L for articaine with epinephrine 1:200,000 and 580 micrograms/L for articaine without epinephrine. The elimination half-time of articaine is about 20 minutes. The rapid breakdown of articaine to the inactive metabolite articainic acid is related to a very low systemic toxicity and consequently to the possibility of repeated injections. Equal analgesic efficacy along with lower systemic toxicity (i.e. a wide therapeutic range) permits the use of articaine in higher concentrations than other amide-type local anaesthetics. Complete anaesthesia can be observed in nearly 90% of all cases, using articaine 4% 60 to 80 mg with epinephrine 1:200,000. Articaine is better able to diffuse through soft tissue and bone than other local anaesthetics. The concentration of articaine in the alveolus of a tooth in the upper jaw after extraction was about 100 times higher than that in systemic circulation. The plasma protein binding rate of articaine and articainic acid is 70%. It has been concluded that an unintentional intravascular injection of articaine 80 mg does not cause toxic effects in healthy individuals.

Alveolar Process↗
PubMed1996

Determination of scopolamine in human serum by gas chromatography-ion trap tandem mass spectrometry.

The objective of this study was to develop a very sensitive and selective method for the determination of scopolamine in serum with a rapid and simple sample preparation. A capillary column gas chromatographic-ion trap tandem mass spectrometric technique has been applied. Scopolamine and the internal standard mexiletine were extracted from serum samples and cleaned up by using a single step liquid-liquid extraction. Derivatization was carried out using 2,2,2-trifluoro-N-methyl-N-trimethylsilylacetamide. The mass spectrometer was operated with positive ions in the selected reaction mode with chemical ionisation using methane. The sum of peak height of two daughter ions was used for quantification. The detection limit was 50 pg/ml in serum.

Cholinergic Antagonists↗
PubMed1996

New sensitive method for the determination of hydrochlorothiazide in human serum by high-performance liquid chromatography with electrochemical detection.

A HPLC method with a very sensitive electrochemical detection has been developed for determining the diuretic agent hydrochlorothiazide (HCT) in serum of volunteers to whom a single dose of the fixed combination of 12.5 mg HCT and 25 mg triamterene was administered. In the present method samples (0.2 ml serum, pH 7) were purified by extraction of HCT into 5 ml tert.-butyl-methyl ether. The separated organic phase was spiked with p-aminobenzoic acid (PABA) standard. The separation was performed on a reversed-phase C18 column using phosphate buffer-acetonitrile (90:10). A coulometric cell was used to measure HCT and an ultraviolet detector for PABA. The limit of quantitation for serum samples of only 200 microliters was 5 ng/ml (i.e. 60 pg HCT/injection) with a good reproducibility (1-8%). Short retention times were found: 1.2 min for PABA and 5.8 min for HCT.

4-Aminobenzoic Acid↗
PubMed1996

Direct demonstration of small intestinal secretion and site-dependent absorption of the beta-blocker talinolol in humans.

OBJECTIVE: To examine the relevance of site-dependent small intestinal absorption for incomplete intestinal absorption of the poorly metabolized beta 1-adrenergic receptor antagonist talinolol. METHODS: The intestinal steady-state perfusion technique (triple lumen tubing system with a 30 cm test segment) for intraluminal measurements was combined with simultaneous determination of talinolol serum concentrations. Dissolved talinolol was perfused over 160 minutes into different parts of the small intestine. The middle of the test segment was located between 25 and 235 cm beyond the teeth. Each of the six healthy subjects was studied twice with a proximal and a more distal site of perfusion to allow for comparisons within an individual subject. RESULTS: The area under the curve for serum concentrations from 0 to 480 minutes [AUC(0-480 min)] and the maximum serum concentration after distal perfusions corresponded to only 15% to 73% and 7% to 90% of the proximal values, respectively. AUC decreased with increasing distance from the teeth. The mean amount of talinolol absorbed from the test segment per unit time (intestinal transport rate) corresponds to only one-tenth of the amount of drug offered to the test segment (perfusion rate). There was a direct correlation between the perfusion rate of talinolol and its transport rate for both regions and in all subjects investigated. However, to achieve the same transport rate in the distal region a higher perfusion rate is required, compared to the proximal small intestine. At perfusion rates lower than 600 micrograms/min, net secretion of talinolol into the intestinal lumen occurred against a steep concentration gradient blood: lumen of about 1:4200. CONCLUSION: Talinolol oral bioavailability of 55% is due to a low absorption rate and a decrease of absorption capabilities along the small intestine. Net absorption of talinolol is reduced by the involvement of active intestinal secretion.

Administration, Oral↗
PubMed1995

Disposition and bioavailability of the beta 1-adrenoceptor antagonist talinolol in man.

In an open randomized crossover study, the pharmacokinetics and bioavailability of the selective beta 1-adrenoceptor antagonist talinolol (Cordanum--Arzneimittelwerk Dresden GmbH, Germany) were investigated in twelve healthy volunteers (five female, seven male; three poor and nine extensive metabolizers of the debrisoquine hydroxylation phenotype) after intravenous infusion (30 mg) and oral administration (50 mg), respectively. Concentrations of talinolol and its metabolites were measured in serum and urine by HPLC or GC-MS. At the end of infusion a peak serum concentration (Cmax) of 631 +/- 95 ng mL-1 (mean +/- SD) was observed. The area under the serum concentration-time curve from zero to infinity (AUC0-infinity) was 1433 +/- 153 ng h mL-1. The following parameters were estimated: terminal elimination half life (t 1/2), 10.6 +/- 3.3 h; mean residence time, 11.6 +/- 3.1 h; volume of distribution, 3.3 +/- 0.5 L kg-1; and total body clearance, 4.9 +/- 0.6 mL min-1 kg-1. Within 36 h 52.8 +/- 10.6% of the administered dose was recovered as unchanged talinolol and 0.33 +/- 0.18% as hydroxylated talinolol metabolites in urine. After oral administration a Cmax of 168 +/- 67 ng mL-1 was reached after 3.2 +/- 0.8 h. The AUC0-infinity was 1321 +/- 382 ng h mL-1. The t 1/2 was 11.9 +/- 2.4 h. 28.1 +/- 6.8% of the dose or 55.0 +/- 11.0% of the bioavailable talinolol was eliminated as unchanged talinolol and 0.26 +/- 0.17% of the dose as hydroxylated metabolites by kidney. The absolute bioavailability of talinolol was 55 +/- 15% (95% confidence interval, 36-69%).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Pharmacokinetics of the antiarrhythmic agent tiracizine: steady state kinetics in comparison with single-dose kinetics.

Serum and urine kinetics of unchanged tiracizine (T), a new class I antiarrhythmic agent, and three metabolites (M1, 2, and 3) were assessed in eight healthy extensive metabolizers after a single oral administration of 50 mg tiracizine and during steady state (50 mg b.i.d.). Additionally, tiracizine-induced ECG changes were measured. Considerable accumulation of M1 and M2 was observed during repeated dosing (M1, Cmax,ss = 391.8 ng mL-1 against Cmax,sd = 132.8 ng mL-1; M2, Cmax,ss = 143.2 ng mL-1 against Cmax,sd = 25.8 ng mL-1). However, significant increases of AUC (AUC tau = 261.9 ng h mL-1 against AUC0-infinity,sd = 182.9 ng h mL-1), Cmax (Cmax,ss = 75.9 ng mL-1 against Cmax,sd = 56.9 ng mL-1) and t 1/2 beta (t 1/2 beta,ss = 4.0 h against t 1/2 beta,sd = 2.4 h) of the parent compound indicate non-linear kinetics. The significant decrease in renal clearance of all four substances as well as the decrease of non-renal tiracizine clearance with repeated dosing led to the assumption that non-linearity is due to saturable renal excretion and a fall in intrinsic tiracizine clearance. PQ time was prolonged significantly during steady state and culminated at the tmax of the parent compound, whereas there was no change in any ECG parameter after a single-dose administration of 50 mg tiracizine.

Administration, Oral↗
PubMed1995

Day-night variations in the renal excretion of the antiarrhythmic agent tiracizine and its metabolites.

Daytime and nighttime urinary recovery as well as morning and evening trough serum levels of the antiarrhythmic agent tiracizine and three of its metabolites (M1, M2, and M3) were assessed during a 7-day multiple-dose study period (50 mg tiracizine twice daily) in eight healthy volunteers. A significantly lower mean steady-state urinary recovery was observed during the daytime as compared with during the nighttime (Ae (tot tau d)=42.0 +/- 15.7% vs. Ae (tot tau n)=51.2 +/- 19.6%). This difference is mainly due to a substantial increase of M1 and a smaller increase of M2 urinary recovery by night. Results of additional in vitro investigations showed the ratio of the nonionic/ionic forms of M1 and M2 to be highly dependent on pH in the range of pH 5-pH 7. Therefore, the observed day-night variations might be attributed to alterations of ionization, i.e., nonionic tubular reabsorption of the metabolites due to circadian differences in urinary pH. Trough serum levels of M1 and M2 tended to be higher at 7 P.M. as compared with 7 A.M. Due to the narrow therapeutic index of class I antiarrhythmics, the present results indicate the need for further investigations concerning the effect of urinary pH on the pharmacokinetics of tiracizine and its metabolites.

Adult↗