Effect of itraconazole on the pharmacokinetics and pharmacodynamics of fexofenadine in subjects with known genotype of MDR1 3435C&gt;T allele

Shon, Ji‐Hong; Lee, I.; Kim, M.; Chun, Huang; Lee, J.; Yoon, Yune‐Jung; Cha, Seong-Sook; Kim, Heonoh; Shin, Jae‐Gook

doi:10.1016/s0009-9236(03)90569-8

Cited by 2 publications

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“…The interaction between fexofenadine and certain transporters was not totally surprising, since it was known that its precursor terfenadine was a substrate/potent inhibitor of P-gp [66]. The increased plasma levels of fexofenadine when co-administered with verapamil, probenecid, erythromycin, itraconazole, ritonavir and St John's wort (single dose) are likely due to interactions with transporters [24,28,[67][68][69]. Interactions with transporters can also reduce exposure to fexofenadine.…”

Section: H1 Antihistamines As Victims Of Drug-drug Interactionsmentioning

confidence: 99%

Development of New H1 Antihistamines: The Importance of Pharmacokinetics in the Evaluation of Safe and Therapeutically Effective Agents

Whomsley¹,

Benedetti

2005

CMCAIAA

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H 1 antihistamines are widely used in the treatment of allergic disorders. The CNS depressant and antimuscarinic effects of the first generation compounds limited their use in allergic disorders, and the second generation compounds were developed to reduce or eliminate these effects. However, the use of the first second generation H1 antihistamines, terfenadine and astemizole, under certain circumstances, was associated with adverse cardiac effects, which were occasionally fatal and they were withdrawn from the market. This review examines the pharmacokinetics of the second generation antihistamines and the impact of the pharmacokinetic properties on their efficacy and safety, particularly with regard to their effects on the central nervous and cardiovascular systems and their potential for interactions with concomitantly administered drugs and dietary components.

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Section: H1 Antihistamines As Victims Of Drug-drug Interactionsmentioning

confidence: 99%

Development of New H1 Antihistamines: The Importance of Pharmacokinetics in the Evaluation of Safe and Therapeutically Effective Agents

Whomsley¹,

Benedetti

2005

CMCAIAA

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Comparison of pharmacokinetics and metabolism of desloratadine, fexofenadine, levocetirizine and mizolastine in humans

Molimard

Diquet

Benedetti

2004

Fundamemntal Clinical Pharma

131

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Absorption, distribution, metabolism and excretion of desloratadine, fexofenadine, levocetirizine, and mizolastine in humans have been compared. The time required to reach peak plasma levels (tmax) is shortest for levocetirizine (0.9 h) and longest for desloratadine (> or =3 h). Steady-state plasma levels are attained after about 6 days for desloratadine, 3 days for fexofenadine, 2-3 days for mizolastine and by the second day for levocetirizine. The apparent volume of distribution is limited for levocetirizine (0.4 L/kg) and mizolastine (1-1.2 L/kg), larger for fexofenadine (5.4-5.8 L/kg) and particularly large for desloratadine (approximately 49 l/kg). Fexofenadine and levocetirizine appear to be very poorly metabolized (approximately 5 and 14% of the total oral dose, respectively). Desloratadine and mizolastine are extensively metabolized. After administration of 14C-levocetirizine to healthy volunteers, 85 and 13% of the radioactivity are recovered in urine and faeces, respectively. In contrast, faeces are the preferential route of excretion for 14C-fexofenadine (80% vs. 11% of the radioactive dose in urine). The corresponding values are 41% (urine) and 47% (faeces) for 14C-desloratadine, 84-95% (faeces) and 8-15% (urine) for 14C-mizolastine. The absolute bioavailability is 50-65% for mizolastine; it is high for levocetirizine as the percentage of the drug eliminated unchanged in the 48 h urine is 77% of the oral dose; the estimation for fexofenadine is at least 33%; no estimation was found for desloratadine. Fexofenadine is a P-glycoprotein (P-gp) substrate and P-gp is certainly involved both in the poor brain penetration by the compound and, at least partially, in a number of observed drug interactions. An interaction of desloratadine with P-gp has been suggested in mice, whereas the information on mizolastine is very poor. The fact that levocetirizine is a substrate of P-gp, although weak in an in vitro model, could contribute to prevent drug penetration into the brain, whereas it is unlikely to be of any clinical relevance for P-gp-mediated drug interactions.

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Effect of itraconazole on the pharmacokinetics and pharmacodynamics of fexofenadine in subjects with known genotype of MDR1 3435C>T allele

Abstract: Clinical Pharmacology & Therapeutics (2003) 73, P58–P58; doi:

Cited by 2 publications

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Development of New H1 Antihistamines: The Importance of Pharmacokinetics in the Evaluation of Safe and Therapeutically Effective Agents

Development of New H1 Antihistamines: The Importance of Pharmacokinetics in the Evaluation of Safe and Therapeutically Effective Agents

Comparison of pharmacokinetics and metabolism of desloratadine, fexofenadine, levocetirizine and mizolastine in humans

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