| DOI: 10.29090/psa.2026.01.25.7009 | Pharm Sci Asia 2026; 53(1), 37-43 |
Impact of CYP1A2 induction on pharmacokinetics of melatoninNuttawut Jenjirattithigarn, Nontaya Nakkam, Sirimas Kanjanawart, Thanawat Kaewkamson, Wichittra Tassaneeyakul*
- Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
Melatonin, a hormone secreted by the pineal gland, regulates circadian rhythm and has been investigated for therapeutic use in conditions linked to altered melatonin levels. However, pharmacokinetic data in the Thai population are limited, and interindividual variability may be influenced by CYP1A2 activity. This study evaluated the pharmacokinetics of melatonin and the effect of CYP1A2 induction in 25 healthy Thai male volunteers. The study was conducted in two phases: a baseline phase to characterize melatonin pharmacokinetics under normal conditions, and a postinduction CYP1A2 induction with 120 mg/day omeprazole for 7 days. An in vivo CYP1A2 activity was assessed using the saliva paraxanthine/caffeine (PX/CA) ratio. In both phases, a single oral dose of 20 mg melatonin was administered, and blood samples were collected at 0, 0.25, 0.5, 1.0, 1.25, 1.5, 2, 3, 4, 5 and 6 hrs post-dose. Plasma melatonin concentrations were quantified using an HPLC-fluorescence technique. Results from the baseline phase showed rapid absorption with a mean maximum concentration (Cmax) of 53.42 ± 49.52 ng/mL, a total area under the curve (AUC0-inf) of 63.10 ± 53.15 ng·h/mL, an apparent clearance (Cl/F) of 8.08 ± 5.23 L/hr·kg, and an elimination half-life (T1/2) of 0.80 ± 0.14 hr. Following omeprazole treatment, the saliva PX/CA ratio increased by approximately 1.77-fold, indicating enhanced in vivo CYP1A2 activity. Concomitantly, both the Cmax and AUC0-inf of melatonin decreased by approximately twofold, to 26.33 ± 34.83 ng/mL and 30.29 ± 28.10 ng·h/mL. In conclusion, CYP1A2 activity appears to play a significant role in modulating bioavailability of melatonin.
Keyword:
Melatonin; Pharmacokinetics; CYP1A2 induction; Bioavailability
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