ABSTRACT
OBJECTIVE: The study was designed to evaluate the effect of hormone therapy (HT) preparations containing 17beta-estradiol and micronized progesterone administered orally and transdermally on the pharmacokinetics of lidocaine, a probe drug that is metabolized by liver oxidative pathways involving cytochrome P-450 1A2 and 3A4 (CYP1A2 and CYP3A4). DESIGN: The study was carried out in 18 postmenopausal women divided into two groups administered HT for 6 months: group 1, 17beta-estradiol (orally) and micronized progesterone sublingually; and group 2, 17beta-estradiol (transdermally) and micronized progesterone sublingually. Pharmacokinetic study with intravenous lidocaine (1 mg/kg) and blood sampling during 360 minutes from injection was performed before the HT initiation and after 3 and 6 months of HT. RESULTS: Pharmacokinetic parameters of lidocaine demonstrated accelerated drug elimination in women on oral HT after 3 months. A significant reduction of area under the curve by 15.0% (P < 0.05), shortening of t(1/2) by 15.2% (P < 0.05), increase of lambda(z) by 10.0% (P < 0.05), and Cl/BW by 14.3% (P < 0.05) were observed. In contrast, transdermal administration of HT did not influence pharmacokinetic parameters of the drug. The effects of oral HT were not seen 6 months after the start of HT. CONCLUSION: HT can influence the pharmacokinetics of lidocaine, ie, its hepatic metabolism, through CYP3A4 and CYP1A2. The effect depends on the route of administration and therapy duration.
