Table 1.
H1 Antihistamines: pharmacokinetics and pharmacodynamics in healthy adults.
Reproduced with permission [5]
| 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 |
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
bOnset/duration of action is based on wheal and flare studies
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