Lidocaine pharmacokinetics in postmenopausal women on hormone therapy.
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).


METHODS
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.


CONCLUSIONS
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.
Gawronska-Szklarz
Barbara
B
Department of Pharmacology, Pomeranian Medical University, Szczecin, Poland.
Zarzycki
Mariusz
M
Musial
Heros David
HD
Pudlo
Artur
A
Loniewski
Igor
I
Drozdzik
Marek
M
D000279:Administration, Cutaneous; D000286:Administration, Sublingual; D000779:Anesthetics, Local / Q000493:pharmacokinetics*; D019540:Area Under Curve; D019388:Cytochrome P-450 CYP1A2 / Q000097:blood / Q000187:drug effects; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000097:blood / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D008012:Lidocaine / Q000493:pharmacokinetics*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D017698:Postmenopause / Q000187:drug effects / Q000378:metabolism*; D011374:Progesterone / Q000008:administration & dosage / Q000378:metabolism*; D012044:Regression Analysis; D013997:Time Factors
D000779:Anesthetics, Local; D011374:Progesterone; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; D008012:Lidocaine; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human