Pharmacodynamic and pharmacokinetics of BW 825C: A new antihistamine

Cohen, Adam F.; Hamilton, M. J.; Liao, Sam; Findlay, J. W. A.; Peck, A. W.

doi:10.1007/bf00609692

Cited by 31 publications

(37 citation statements)

References 10 publications

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“…These considerations led us to carry out the present clinical pharmacological study in healthy volunteers. Pharmacodynamics consisted of intradermal histamineinduced wheal and flare and subjective reactivity for evaluating peripheral H 1 antihistamine activity [25][26][27], together with standard objective laboratory tests measuring drug effects on a variety of mental functions [28][29][30][31] and subjective reports on visual analogue scales (VAS) which are validated measures of subjective experience, e.g. sedation or tiredness [32][33][34].…”

Section: Introductionmentioning

confidence: 99%

Central and Peripheral Evaluation of Rupatadine, a New Antihistamine/Platelet-Activating Factor Antagonist, at Different Doses in Healthy Volunteers

et al. 2004

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Aims: To assess peripheral anti-H₁ and central nervous system (CNS) activity of single increasing doses of rupatidine fumarate (RU), a new antihistamine/platelet-activating factor antagonist compound, in comparison with hydroxyzine and placebo. Methods: Eighteen healthy young subjects of both sexes took part in a crossover, randomised, double-blind, placebo-controlled study. Treatments tested were: RU 10, 20, 40 and 80 mg and hydroxyzine 25 mg, as a positive standard. Before and several times after drug intake, peripheral anti-H₁ activity was appraised by the skin reactivity to intradermal injection of histamine. CNS effects were also obtained by objective tests of psychomotor performance and subjective mood scales. Results: All active treatments showed a significant reduction of the wheal and flare reaction in relation to placebo, RU displaying a potent dose-dependent inhibition pattern. The global nonparametric Friedman test to changes from placebo in 15 objective variables from psychomotor performance showed a significant impairment of similar magnitude after hydroxyzine 25 mg (p = 0.01) and RU 80 mg (p = 0.02), but this was slower in development and recovery after the latter. After RU 40 mg, a smaller impairment was also obtained (p = 0.04). Activity (p = 0.01) and drowsiness (p = 0.02) scales showed significant changes, the subjects feeling less active and more drowsy after all active treatments. Conclusion: RU presents a potent dose-dependent peripheral anti-H₁ activity, displaying psychomotor impairment activity only at the highest dose (80 mg), while therapeutically relevant lower doses (10 and 20 mg) were similar to placebo.

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Section: Introductionmentioning

confidence: 99%

Central and Peripheral Evaluation of Rupatadine, a New Antihistamine/Platelet-Activating Factor Antagonist, at Different Doses in Healthy Volunteers

et al. 2004

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“…The attenuation of the pain sensation parallels the inhibition of the histamine wheal response and suggests that both the wheal and pain are related by histamine. Histamine-induced wheal is a standard test for assessing the antihistamine effect of drugs (Huther et al, 1977;Carruthers et al, 1978;Bateman et al, 1983;Cohen et al, 1985;Levander et al, 1985). The inhibition of skin wheal appears to be a quantitative index for assessing both drug concentration and the timecourse of drug action.…”

Section: Discussionmentioning

confidence: 99%

The pharmacokinetics, antihistamine and concentration‐effect relationship of ebastine in healthy subjects.

Vincent

Liminana

Meredith

et al. 1988

Brit J Clinical Pharma

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1. The kinetics and effects of ebastine 10 and 50 mg were studied after oral dosing in healthy subjects. 2. The parent drug was extensively metabolised during the first pass to its carboxylic acid derivative, carebastine. 3. The pharmacokinetics of carebastine were linear over the dose range studied and the terminal elimination half‐life was 10.6 +/‐ 2.6 and 12.5 +/‐ 1.9 h respectively after 10 and 50 mg of ebastine. 4. Antihistamine (H1‐receptor) activity was examined with intradermal histamine (2 micrograms). Oral ebastine reduced the histamine wheal area for up to 24 h and also reduced subjective local pain. 5. Antihistamine activity correlated well with plasma levels of carebastine in individual subjects. 6. Ebastine appears to have potential as an antihistamine for once a day dosing.

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“…Most first‐generation antihistamines have good oral absorption because of their liposolubility, achieving their maximum plasma concentration (C max ) and therefore therapeutic effects within 2‐3 hours . Results of historical PK assessments of oral triprolidine are presented in Table …”

Section: Pharmacokinetics Of Oral Triprolidine From Historical Human mentioning

confidence: 99%

Bioavailability of Triprolidine as a Single Agent or in Combination With Pseudoephedrine: A Randomized, Open‐Label Crossover Study in Healthy Volunteers

Febbraro¹,

Shea

Cravo

2020

Clinical Pharm in Drug Dev

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Antihistamines have been in clinical use for more than 70 years to treat allergic and nonallergic symptoms including relief from cold and flu symptoms. Despite their widespread use, pharmacokinetic (PK) data are sparse for older, first-generation antihistamines. This phase 1 single-center open-label, randomized, single-dose, 3-way crossover trial evaluated the PK profiles of 2 doses of film-coated triprolidine caplets (2.5 and 5 mg) compared with a reference combination tablet (triprolidine 2.5 mg + pseudoephedrine 60 mg) in 24 healthy adults. Blood samples were collected predose and at specified intervals across a 24-hour period after administration, and triprolidine was quantified using liquid chromatography-tandem mass spectrometry. Maximum plasma concentration of triprolidine for the 2.5 mg and dose-normalized 5 mg single-agent tablets were comparable (8.4 versus 7.1 ng/mL, respectively) and higher for the combination tablet (9.5 ng/mL). PK parameters, including time to maximum plasma concentration (ß1.5 hours) and elimination half-life (ß4 hours), were comparable between the 3 treatment arms. The safety profile of this sedating antihistamine was as expected; however, adverse effects were reported in a markedly higher proportion of women than men. There were no significant sex differences in any of the measured PK parameters.

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Pharmacodynamic and pharmacokinetics of BW 825C: A new antihistamine

Cited by 31 publications

References 10 publications

Central and Peripheral Evaluation of Rupatadine, a New Antihistamine/Platelet-Activating Factor Antagonist, at Different Doses in Healthy Volunteers

Central and Peripheral Evaluation of Rupatadine, a New Antihistamine/Platelet-Activating Factor Antagonist, at Different Doses in Healthy Volunteers

The pharmacokinetics, antihistamine and concentration‐effect relationship of ebastine in healthy subjects.

Bioavailability of Triprolidine as a Single Agent or in Combination With Pseudoephedrine: A Randomized, Open‐Label Crossover Study in Healthy Volunteers

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