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Table 1 H1 Antihistamines: pharmacokinetics and pharmacodynamics in healthy adults.

From: CSACI position statement: Newer generation H1-antihistamines are safer than first-generation H1-antihistamines and should be the first-line antihistamines for the treatment of allergic rhinitis and urticaria

Orally administered H1-antihistamines Time to maximum plasma concentration (h) after a single dose Terminal elimination half-life (h) Clinically relevant drug–drug interactionsa Onset of action (h)b Duration of action (h)b
First (old) generation
 Chlorpheniraminec 2.8 ± 0.8 27.9 ± 8.7 Possible 3 24
 Diphenhydraminec 1.7 ± 1.0 9.2 ± 2.5 Possible 2 12
 Doxepinc 2 13 Possible NA NA
 Hydroxyzinec 2.1 ± 0.4 20 ± 4.0 Possible 2 24
Second (new) generation
 Bilastine 1.2 14.5 Unlikely 2 24
 Cetrizine 1.0 ± 0.5 6.5–10 Unlikely 0.7 ≥ 24
 Desloratidine 1.0–3.0 27 Unlikely 2–2.6 ≥ 24
 Fexofenadinea 1.0–3.0 11.0–15.0 Unlikely 1.0–3.0 24
 Levocetirizine 0.8 ± 0.5 7 ± 1.5 Unlikely 0.7 > 24
 Loratidine (metabolite: descarboethoxyloratidine) 1.2 ± 0.3 (1.5 ± 0.7) 7.8 ± 4.2 (24 ± 9.8) Unlikely 2 24
 Rupatadine 0.75–1.0 6 (4.3–14.3) Unlikely 2 24
  1. aClinically relevant drug–drug interactions are unlikely with most of the 2nd generation H1-antihistamines. Clinically relevant drug-food interactions have been well studied for fexofenadine. Naringin, a flavonoid found in grapefruit juice, and hesperidin, a flavonoid in orange juice, reduce the oral bioavailability of fexofenadine through the inhibition of OATP 1A2. This interaction can be avoided by waiting for 4 h between juice ingestion and fexofenadine dosing
  2. bOnset/duration of action is based on wheal and flare studies
  3. cSix or seven decades ago, when many of the first-generation H1-antihistamines were introduced, pharmacokinetic and pharmacodynamic studies were not required by regulatory agencies. They have subsequently been performed for some of these drugs; however, empiric dosage regimens persist. For example, the manufacturers’ recommended diphenhydramine dose for allergic rhinitis is 25 to 50 mg every 4 to 6 h, and the diphenhydramine dose for insomnia is 25 to 50 mg at bedtime. Despite the long terminal elimination half-life values identified for some of the medications (e.g., > 24 h for chlorpheniramine), based on tradition, extended release formulations remain in use