Absorption pattern of trospium chloride along the human gastrointestinal tract assessed using local enteral administration

Schröder, Sven; Jetter, Alexander; Zaigler, M; Weyhenmeyer, Roland; Krumbiegel, Günter; Wächter, W; Fuhr, Uwe

doi:10.5414/cpp42543

Cited by 18 publications

(14 citation statements)

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“…4. After the oral administration 40 mg of the TCL tablets or capsules to the volunteers, pharmacokinetic data for TCL meet to those reported in the literature (Schroder et al 2004). The C max , T max , and T 1=2 were similar to and equivalent among the formulations (Table 1).…”

Section: Bioequivalence Studymentioning

confidence: 53%

“…Approximately 80% of the absorbed fraction is renally eliminated as unchanged drug via active tubular secretion, and 15% is hepatically metabolized into spiroalcohol and hydrolysis=oxidation products (Schroder et al 2004;Halaska et al 2003). The TCL has the advantage of not being metabolized by the cytochrome P450 (CYP450) system in the liver, which should eliminate clinically relative drug interactions related to the metabolism of TCL.…”

Section: Bioequivalence Studymentioning

confidence: 98%

“…More recently, sensitive assays for quantitative determination of TCL in human plasma and urine have been developed. Quantification of TCL and its major metabolite in biological specimens can be achieved using high-performance liquid chromatography (HPLC) with fluorometric detection (Spahn et al 1984;Schladitz-Keil, Spahn, and Mutschler 1985), radioimmunoassay (Lehtola, Lavikainen, and Huhtikangas 1988), and gas chromatography-mass spectrometry (GC-MS) (Schroder et al 2004;Doroshyenko et al 2005) with lower limits of quantification of 0.5-1.0 ng=ml. However, these published methods are not ideal for a large number of sample determinations, because they are time consuming or costly, i.e., arduous sample preparation, long chromatographic run times.…”

Section: Introductionmentioning

confidence: 99%

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High-Performance Liquid Chromatography-Tandem Mass Spectrometry for the Determination of Trospium Chloride in Human Plasma and Its Application in a Bioequivalence Study

et al. 2011

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A selective, rapid, and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-ESI-MS/MS) method was developed and validated for the quantification of trospium chloride in human plasma. With tramadol chloride as the internal standard, sample pretreatment involved a simple liquid-liquid extraction with chloroformisopropyl alcohol (40/2, v=v) of 0.5 ml plasma. The analysis was carried out on a Hypsil C 18 column (150 mm Â 2.1 mm, 5.0 lm) with a flow rate of 0.2 ml/min. The mobile phase was methanol-5% acetic acid-20 mM ammonium methylate (55/30/15, v/v/v). The detection was performed by a selected reaction monitoring (SRM) mode via electrospray ionization (ESI). Linear calibration curves were obtained in the concentration range of 0.2-50.0 ng/ml, with a lower limit of quantification of 0.2 ng/ml. The intra-and inter-day precision (RSD) values were below 15%. The method was successfully applied to a clinical bioequivalence study of trospium chloride in Chinese healthy volunteers following oral administration.

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Section: Bioequivalence Studymentioning

confidence: 53%

Section: Bioequivalence Studymentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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High-Performance Liquid Chromatography-Tandem Mass Spectrometry for the Determination of Trospium Chloride in Human Plasma and Its Application in a Bioequivalence Study

et al. 2011

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“…The enteric coated tablets also generated maximum plasma concentrations after being absorbed from the wider window following a lag time of ∼2 to 3 hours. Bioavailability was ∼20% lower . Second, the major prokinetic effect of clarithromycin is most likely not or only slightly overshadowed by inhibition of intestinal P‐gp.…”

Section: Discussionmentioning

confidence: 99%

Effects of the P‐Glycoprotein Inhibitor Clarithromycin on the Pharmacokinetics of Intravenous and Oral Trospium Chloride: A 4‐Way Crossover Drug‐Drug Interaction Study in Healthy Subjects

Abebe

Weiß

Modeß

et al. 2019

The Journal of Clinical Pharma

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The quaternary ammonium compound trospium chloride is poorly absorbed from 2 “absorption windows” in the jejunum and cecum/ascending colon, respectively. To confirm whether intestinal P‐glycoprotein (P‐gp) is involved, a 4‐period, crossover drug interaction study with trospium chloride after intravenous (2 mg) and oral administration (30 mg) without and after comedication of clarithromycin (500 mg), an inhibitor for P‐gp, was initiated in 12 healthy subjects. Pharmacokinetics of trospium was evaluated using gas chromatography–mass spectrometry, noncompartmental evaluation, and pharmacokinetic modeling. Trospium chloride was poorly absorbed after oral administration (absolute bioavailability, ∼8%–10%). About 30% of the bioavailable dose fraction was absorbed from the “narrow window”. Comedication with clarithromycin increased steady‐state distribution volumes by ∼27% (P < .01). Bioavailability was not increased as hypothesized. The geometric mean ratios (90% confidence interval) for area under the plasma concentration–time curve, maximum concentration, and renal clearance accounted for 0.75 (0.56–1.01), 0.64 (0.45–0.89), and 1.00 (0.90–1.13), respectively. The amount of trospium absorbed from the “narrow window” was reduced in all subjects but from the “wider window” in only 9 of them. Bioavailability was strongly predicted by the maximum absorption rate of trospium in the distal “window” (rs2 = 0.910, P < .0001). In conclusion, the P‐gp inhibitor clarithromycin significantly increases distribution volumes but not oral absorption of trospium. The amount absorbed from the “narrow window” was lowered in all subjects. However, the extent of all influences seems not to be of clinical relevance.

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“…However, in a recent large trial, the rate of discontinuation for adverse events (including dry mouth) was not appreciably different from that noted in trials of other anticholinergics [75]. A disadvantage of trospium is its low and variable bioavailability, owing to poor absorption of the drug from the lower gastrointestinal tract [76].…”

Section: Newer Anticholinergic Optionsmentioning

confidence: 99%

The puzzle of overactive bladder: controversies, inconsistencies, and insights

Dmochowski

2006

Int Urogynecol J

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Overactive bladder (OAB) affects millions of individuals and may severely impair the quality of life of those affected. The contribution of human behavior to manifestations of this symptom complex remains poorly understood. Continued evolution of our understanding of the pathophysiology of OAB has identified contributory mechanisms, which in turn may open new therapeutic avenues. Recent improvements in drug delivery systems represent advances in the management of OAB. However, more complete symptom control with greater tolerability is desirable; this awaits the development of agents specific for newly emerging and as yet unidentified pathophysiologic pathways. Importantly, as understanding of outcomes assessment in OAB matures, refined assessments of disease severity, response to intervention, and patient preference should be possible.

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Absorption pattern of trospium chloride along the human gastrointestinal tract assessed using local enteral administration

Cited by 18 publications

References 0 publications

High-Performance Liquid Chromatography-Tandem Mass Spectrometry for the Determination of Trospium Chloride in Human Plasma and Its Application in a Bioequivalence Study

High-Performance Liquid Chromatography-Tandem Mass Spectrometry for the Determination of Trospium Chloride in Human Plasma and Its Application in a Bioequivalence Study

Effects of the P‐Glycoprotein Inhibitor Clarithromycin on the Pharmacokinetics of Intravenous and Oral Trospium Chloride: A 4‐Way Crossover Drug‐Drug Interaction Study in Healthy Subjects

The puzzle of overactive bladder: controversies, inconsistencies, and insights

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