Determination of tolterodine and the 5-hydroxymethyl metabolite in plasma, serum and urine using gas chromatography-mass spectrometry

Palmér, Lena; Andersson, Lars; Andersson, Tommy; Stenberg, Ulf

doi:10.1016/s0731-7085(97)00023-x

Cited by 41 publications

(27 citation statements)

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“…At the end of the study, the urinary flow rate and residual volume were re-measured; the subjective improvement that each patient gained from treatment was determined by a 'yes/no' answer to the question 'Have you had any benefit from treatment? 'Venous blood samples were drawn up to 3 h after administering the first dose on day 1 and up to 8 h after the first dose on day 14 to determine serum tolterodine and 5-HM levels, using liquid chromatography/mass spectrometry [16]. Further blood samples were drawn for genotyping and determining the levels of a 1 -acid glycoprotein (AGP, day 14 only).…”

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confidence: 99%

The overactive bladder in children: a potential future indication for tolterodine

et al. 2001

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Objective To determine the safety, efficacy and pharmacokinetics of tolterodine in children with an overactive bladder. Patients and methods Thirty-three children (20 boys and 13 girls, aged 5-10 years) with an overactive bladder and symptoms of urgency, frequency and/or urge incontinence were enrolled in an open, dose-escalation study. Patients were treated with oral tolterodine 0.5 mg (n=11), 1 mg (n=10) or 2 mg (n=12) twice daily for 14 days. The primary safety endpoint was the change in residual urinary volume, as determined by ultrasonography. In addition, voiding diary variables (frequency and incontinence episodes) and pharmacokinetics were evaluated. Other safety endpoints included laboratory variables, electrocardiogram recordings and reported adverse events. Results There were no safety concerns in terms of the change in residual urinary volume for any of the three dosage groups; values were comparable with baseline after 2 weeks of treatment for all three dosages. Adverse events were reported by 20 patients (six on 0.5 mg, five on 1 mg, and nine on 2 mg). Most adverse events were not considered to be drug-related; of the 13 possibly related events, 10 occurred in those taking 2 mg. Headache was the most commonly reported adverse event. No serious adverse events were reported and there were no general safety concerns.There was an improvement in voiding diary variables in all treatment groups after 2 weeks of treatment, although the efficacy was greatest in those taking 1 mg and 2 mg. Pharmacokinetic findings were consistent with dose linearity over the range 0.5-2 mg. Conclusion The results support the use of 1 mg twice daily as the optimal dose of tolterodine for treating children aged 5-10 years with an overactive bladder. Keywords tolterodine, antimuscarinic agents, children, overactive bladder, dose-finding study IntroductionThe symptoms of an overactive bladder are urgency and frequency, with or without urge incontinence, caused by uncontrolled contractions of the detrusor muscle. As uncontrolled detrusor contractions are mediated by muscarinic receptor stimulation, antimuscarinic agents are the most frequently used medications for treating this condition [1]. Historically, antimuscarinic agents like oxybutynin have been effective for treating the overactive bladder but they are poorly tolerated because they are not selective for the bladder [2]. Side-effects on the parotid gland, CNS, gastrointestinal tract and on the eye limit their clinical usefulness [3]. Particularly frequent and troublesome is dry mouth, which has been shown to cause poor compliance and frequent discontinuation of treatment [1,[4][5][6].Tolterodine is a muscarinic receptor antagonist that has been shown to be effective for treating the overactive bladder [7][8][9]. The advantages of tolterodine are numerous and are ascribed to its selectivity for the bladder over other tissues and to its low lipophilicity. Differences between tolterodine and oxybutynin have been reported in several preclinical studies, including pharmacologi...

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The overactive bladder in children: a potential future indication for tolterodine

et al. 2001

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“…These methods are developed by spectrophotometry, high performance liquid chromatography, gas chromatography-mass spectrometry, and capillary electrophoresis techniques (9)(10)(11)(12). The techniques require sophisticated instruments or rigorous sample preparation procedures.…”

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confidence: 99%

Spectrofluorimetric Method for the Determination of Tolterodine In Human Plasma and Pharmaceutical Preparations by Derivatization with Dansyl Chloride

Tekkeli¹

2017

Bezmialem Science

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Objective: Tolterodine (TOL) is an anti-muscarinic drug used for the symptomatic treatment of urinary incontinence. Analytical methods in the literature are not sensitive enough for the assay of drug substance biological fluids. To make up the deficit, we developed a sensitive, costreduced spectrofluorimetric method for the determination of TOL in plasma and pharmaceutical preparations.Methods: TOL has a phenolic hydroxyl group that reacts with dansyl chloride. The spectrofluorimetric method is based on this reaction in the presence of a bicarbonate solution of pH 9.5 to give a highly fluorescent derivative, which can be measured at 590 nm with an excitation wavelength at 360 nm in dichloromethane. Different experimental parameters affecting fluorescence intensity were optimized. The relationship between fluorescence intensity and TOL concentration was investigated. Results:The developed method is linear in the concentration range of 5-60 ng mL −1 with a minimum detectability of 0.136 ng mL −1 . The recovery was 100.48%. Conclusion:A simple, cost-effective, and sensitive spectrofluorimetric method was developed and validated for the determination of TOL in human plasma and pharmaceutical preparations using dansyl chloride. According to this validation study, it is possible to use this proposed method for the routine analysis of the drug and for conducting bioavailability and bioequivalence studies with good accuracy and precision.

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“…1), is a new, potent and competitive muscarinic receptor antagonist in clinical development for the treatment of urge incontinence and other symptoms of unstable bladder (1)(2)(3). Tolterodine has a high affinity and specificity for muscarinic receptors in vitro and exhibits the selectivity for the urinary bladder over salivary glands in vivo, so it has the advantageous tolerability profile in terms of the low frequency of bothersome dry mouth (4).…”

Section: Introductionmentioning

confidence: 99%

Comparative in vitro assessment of tolterodine tartrate tablets by high performance liquid chromatographic (HPLC)

Danafar

2016

mazums-pbr

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Determination of tolterodine and the 5-hydroxymethyl metabolite in plasma, serum and urine using gas chromatography-mass spectrometry

Cited by 41 publications

References 0 publications

The overactive bladder in children: a potential future indication for tolterodine

The overactive bladder in children: a potential future indication for tolterodine

Spectrofluorimetric Method for the Determination of Tolterodine In Human Plasma and Pharmaceutical Preparations by Derivatization with Dansyl Chloride

Comparative in vitro assessment of tolterodine tartrate tablets by high performance liquid chromatographic (HPLC)

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