Carboxyterfenadine antacid interaction monitoring by UV spectrophotometry and RP-HPLC techniques
3
Citation
21
Reference
10
Related Paper
Citation Trend
Abstract:
Carboxyterfenadine, a primary metabolite of terfenadine, a second generation antihistaminic compound was introduced in therapy as a successor of terfenadine due to its cardiac arrhythmia. There are number of drug interactions of fexofenadine with erythromycin, ketoconazole and alike reported in the literature. In this paper, fexofenadine antacid interaction has been studied in presence of sodium bicarbonate, megaldrate, calcium carbonate, magnesium carbonate, aluminum hydroxide, magnesium hydroxide, magnesium trisilicate, simethicone (dimethylpolysiloxane) and calcium hydroxide by UV–Vis spectrophotometer and high performance liquid chromatography (HPLC). These in vitro fexofenadine–antacid interactions were carried out in simulated gastric and intestinal juices and in buffer of pH 7.4 (simulating blood pH) on BP 2005 dissolution apparatus. The results show non-concordant availability of fexofenadine envisaged due to formation of unstable charge transfer complexes.Keywords:
Antacid
Fexofenadine
Terfenadine
Spectrophotometry
Fexofenadine
Terfenadine
Histamine H1 Antagonists
Cite
Citations (84)
Fexofenadine
Terfenadine
Tryptase
Cite
Citations (20)
Chronic urticaria defined as repeated or daily eruptions of wheals within a week over a period of at least 1 1/2 months is a frustrating problem not only for the patient but also for the physician. Since a cause will seldom be identified, therapy is symptomatic. In this study the effect of fexofenadine the active metabolite of terfenadine on pruritus, wheal formation and subjective feedbacks has been investigated in 21 patients with chronic urticaria. The study was double-blind, placebo-controlled designed. Following a 1-week washout period all study subjects received fexofenadine 180 mg OD for 3 weeks; thereafter the subjects were randomized for another 3 weeks in a placebo and fexofenadine arm. This study showed that fexofenadine had a beneficial effect on urticaria, particularly pruritus, and the patient-reported symptoms. Reports on side effects were non characteristic and not different between fexofenadine and placebo. Prolongation of QTc intervals or other cardiac side effects have not been observed. Fexofenadine 180 mg is a new antihistamine that is effective in the treatment of chronic urticaria and that has a profile of side effects similar to placebo.
Fexofenadine
Terfenadine
Cite
Citations (10)
P-glycoprotein (P-gp) plays an important role in determining net brain uptake of fexofenadine. Initial in vivo experiments with 24-h subcutaneous osmotic minipump administration demonstrated that fexofenadine brain penetration was 48-fold higher in mdr1a(–/–) mice than in mdr1a(+/+) mice. In contrast, the P-gp efflux ratio at the blood-brain barrier (BBB) for fexofenadine was only ∼4 using an in situ brain perfusion technique. Pharmacokinetic modeling based on the experimental results indicated that the apparent fexofenadine P-gp efflux ratio is time-dependent due to low passive permeability at the BBB. Fexofenadine brain penetration after terfenadine administration was ∼25- to 27-fold higher than after fexofenadine administration in both mdr1a(+/+) and mdr1a(–/–) mice, consistent with terfenadine metabolism to fexofenadine in murine brain tissue. The fexofenadine formation rate after terfenadine in situ brain perfusion was comparable with that in a 2-h brain tissue homogenate in vitro incubation. The fexofenadine formation rate increased ∼5-fold during a 2-h brain tissue homogenate incubation with hydroxyl-terfenadine, suggesting that the hydroxylation of terfenadine is the rate-limiting step in fexofenadine formation. Moreover, regional brain metabolism seems to be an important factor in terfenadine brain disposition and, consequently, fexofenadine brain exposure. Taken together, these results indicate that the fexofenadine BBB P-gp efflux ratio has been underestimated previously due to the lack of complete equilibration of fexofenadine across the blood-brain interface under typical experimental paradigms.
Fexofenadine
Terfenadine
Efflux
Microdialysis
Cite
Citations (0)
Fexofenadine
Terfenadine
Active metabolite
Cite
Citations (39)
Fexofenadine
Terfenadine
P-glycoprotein
Cite
Citations (2)
Chronic urticaria defined as repeated or daily eruptions of wheals within a week over a period of at least 1 1/2 months is a frustrating problem not only for the patient but also for the physician. Since a cause will seldom be identified, therapy is symptomatic. In this study the effect of fexofenadine the active metabolite of terfenadine on pruritus, wheal formation and subjective feedbacks has been investigated in 21 patients with chronic urticaria. The study was double-blind, placebo-controlled designed. Following a 1-week washout period all study subjects received fexofenadine 180 mg OD for 3 weeks; thereafter the subjects were randomized for another 3 weeks in a placebo and fexofenadine arm. This study showed that fexofenadine had a beneficial effect on urticaria, particularly pruritus, and the patient-reported symptoms. Reports on side effects were non characteristic and not different between fexofenadine and placebo. Prolongation of QTc intervals or other cardiac side effects have not been observed. Fexofenadine 180 mg is a new antihistamine that is effective in the treatment of chronic urticaria and that has a profile of side effects similar to placebo.
Fexofenadine
Terfenadine
Cite
Citations (4)
(1) Fexofenadine, a non anticholinergic non sedative antihistamine, is available in France for oral treatment of allergic rhinitis and chronic urticaria. (2) Fexofenadine is actually an active metabolite of terfenadine, a drug taken off the market because of its cardiotoxicity. (3) In seasonal allergic rhinitis a comparative trial showed that the effect of fexofenadine (120 mg/day in a single intake) was moderate and not different from that of cetirizine. (4) In chronic urticaria a dose-finding study showed that the optimal oral dose of fexofenadine was 180 mg/day. The lack of comparative trials means that the efficacy of fexofenadine in relation to other antihistamines is not known. (5) Fexofenadine seems to be well tolerated. Animal studies and limited clinical experience have failed to detect any cardiotoxicity.
Fexofenadine
Terfenadine
Cetirizine
Cardiotoxicity
Desloratadine
Levocetirizine
Cite
Citations (1)
Atorvastatin does not Produce a Clinically Significant Effect on the Pharmacokinetics of Terfenadine
The effect of atorvastatin, a CYP3A4 substrate, on the pharmacokinetics of terfenadine and its carboxylic acid metabolite, fexofenadine, were evaluated. Single 120‐mg doses of terfenadine were given 2 weeks apart to healthy volunteers with 80‐mg daily doses of atorvastatin administered from 7 days before through 2 days after the second terfenadine dose. Concentrations of terfenadine and fexofenadine were measured for 72 hours after each terfenadine dose. Administration of terfenadine alone or in combination with atorvastatin produced no alterations in the QTc interval. For terfenadine, atorvastatin coadministration produced an 8% decrease in maximum concentration (C max ), a 35% increase in area under the concentration‐time curve extrapolated to infinity (AUC 0‐∞ ), and a 2% decrease in elimination half‐life (t 1/2 ). For fexofenadine, atorvastatin coadministration produced a 16% decrease in C max , a 2% decrease in AUC 0‐∞ , and a 51% increase in t 1/2 . None of these changes achieved statistical significance. Coadministration of atorvastatin with terfenadine does not result in a clinically significant drug interaction. Because 80 mg is the highest atorvastatin dose used clinically, drug interactions mediated by CYP3A4 inhibition are unlikely in clinical practice.
Terfenadine
Fexofenadine
Grapefruit juice
Pharmacodynamics
Cite
Citations (22)
P-glycoprotein (P-gp) plays an important role in determining net brain uptake of fexofenadine. Initial in vivo experiments with 24-h subcutaneous osmotic minipump administration demonstrated that fexofenadine brain penetration was 48-fold higher in mdr1a(–/–) mice than in mdr1a(+/+) mice. In contrast, the P-gp efflux ratio at the blood-brain barrier (BBB) for fexofenadine was only ∼4 using an in situ brain perfusion technique. Pharmacokinetic modeling based on the experimental results indicated that the apparent fexofenadine P-gp efflux ratio is time-dependent due to low passive permeability at the BBB. Fexofenadine brain penetration after terfenadine administration was ∼25- to 27-fold higher than after fexofenadine administration in both mdr1a(+/+) and mdr1a(–/–) mice, consistent with terfenadine metabolism to fexofenadine in murine brain tissue. The fexofenadine formation rate after terfenadine in situ brain perfusion was comparable with that in a 2-h brain tissue homogenate in vitro incubation. The fexofenadine formation rate increased ∼5-fold during a 2-h brain tissue homogenate incubation with hydroxyl-terfenadine, suggesting that the hydroxylation of terfenadine is the rate-limiting step in fexofenadine formation. Moreover, regional brain metabolism seems to be an important factor in terfenadine brain disposition and, consequently, fexofenadine brain exposure. Taken together, these results indicate that the fexofenadine BBB P-gp efflux ratio has been underestimated previously due to the lack of complete equilibration of fexofenadine across the blood-brain interface under typical experimental paradigms.
Fexofenadine
Terfenadine
P-glycoprotein
Efflux
Microdialysis
Cite
Citations (34)