Drugs online research references
Clin Pharmacol Ther. 1997 Mar;61(3):325-30.
Pharmacokinetics and pharmacodynamics of cetirizine in infants and toddlers.
Spicak V, Dab I, Hulhoven R, Desager JP, Klanova M, de Longueville M, Harvengt C.
Hospital Bulovka, Prague.
The pharmacokinetics of the second generation H1-receptor antagonist cetirizine were studied in 15 infants and toddlers (mean +/- SD age, 12.3 +/- 5.4 months) who were treated with a single 0.25 mg/kg dose of cetirizine solution. The infants and toddlers were hospitalized for recurrent respiratory infections or other hypersensitivity-related diseases. Blood samples were collected at 1/2, 1, 11/2, 2, 4, 6, 8, 12, and 24 hours, and a 24-hour urine sample was obtained. A peak plasma level of 390 +/- 135 ng/ml was observed after 2.0 +/- 1.3 hours. The elimination half-life was 3.1 +/- 1.8 hours, the apparent oral body clearance was 2.13 +/- 1.15 ml/min/kg, and the apparent volume of distribution was 0.44 +/- 0.19 L/kg. The excretion of unchanged cetirizine in six complete urinary collections was 62.7% +/- 13.2% of the administered dose. An additional pharmacodynamic study (inhibition of the histamine-induced wheal and flare) was performed in 10 of these infants and toddlers, after the intake of 0.25 mg/kg cetirizine twice a day for at least 4 days. A 90% +/- 12% inhibition of the wheal and a 87% +/- 17% inhibition of the flare were still observed 12 hours after the last intake. The duration of the H1-inhibition by cetirizine at the cutaneous level is thus longer in infants and toddlers than could be inferred from its pharmacokinetics; the level of inhibition at 12 hours was the same as in older age groups.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9084458&dopt=Abstract
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Int Arch Allergy Immunol. 1997 May-Jul;113(1-3):339-41.
G proteins as biological targets for anti-allergic drugs?
Rihoux JP, Masliah J, Bereziat G, Konig W.
UCB SA, Braine-l'Alleud, Belgium.
The inhibiting effect of the H1 antihistamine cetirizine on the release of mediators (LTB4, arachidonic acid and phospholipase A2) was measured in different cells in vitro (human PMN, deltaF508 cells, chinese hamster ovary cells and rabbit chondrocytes) using different agonists (fMLP, NaF, calcium ionophore A 23187, bradykinin, adrenaline and IL-1). It was shown that physiological concentrations of the drug inhibited the release when activation of receptor-coupled G proteins was involved. By contrast, there was no inhibiting effect of cetirizine when the release was induced by a calcium ionophore which bypasses the G proteins coupled to cell membrane receptors.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9130571&dopt=Abstract
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Ann Allergy Asthma Immunol. 1997 Jun;78(6):581-5.
Inhibitory effect of cetirizine on cytokine-enhanced in vitro eosinophil survival.
Sedgwick JB, Busse WW.
Department of Medicine, University of Wisconsin, Madison, USA.
BACKGROUND: Cetirizine is an antihistamine that inhibits in vivo eosinophil influx into the inflamed airways following allergen challenge, and in vitro eosinophil chemotaxis and adhesion. Since eosinophils are proposed to have an important role in the pathophysiology of asthma and allergic disease, the effects of cetirizine on eosinophil function may be a mechanism of this agent's therapeutic regulation of the allergic reaction. OBJECTIVE: To determine the effect of cetirizine on in vitro eosinophil survival. METHODS: Using human eosinophils isolated from patients with allergic rhinitis, the cells were cultured in vitro for 48 to 72 hours with medium, cetirizine, or dexamethasone in the presence of IL-5, IL-3, or GM-CSF. Eosinophil survival was assessed by trypan blue exclusion. RESULTS: In the presence of IL-5, but not GM-CSF or IL-3 100 microM cetirizine significantly inhibited eosinophil survival at 48 and 72 hours; the magnitude of this inhibition was dependent on cytokine concentration. Although cetirizine significantly suppressed cytokine promotion of eosinophil survival, it was not as potent as dexamethasone. CONCLUSIONS: Although the in vitro concentration of cetirizine was required to be quite high, cetirizine may affect in vivo airway inflammation through its inhibition of IL-5-dependent eosinophil survival.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9207722&dopt=Abstract
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